dbSNP rs9349626: EFHC1:c.573+10A>G (chr6-52438601-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018100.4(EFHC1):c.573+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,142 control chromosomes in the GnomAD database, including 37,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3237 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34176 hom. )

Consequence

EFHC1
NM_018100.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.190

Publications

5 publications found

Variant links:

Genes affected

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

EFHC1 Gene-Disease associations (from GenCC):

juvenile myoclonic epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

EFHC1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_018100.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-52438601-A-G is Benign according to our data. Variant chr6-52438601-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFHC1	NM_018100.4	MANE Select	c.573+10A>G	intron	N/A	NP_060570.2	Q5JVL4-1
EFHC1	NM_001172420.2		c.516+10A>G	intron	N/A	NP_001165891.1	Q5JVL4-3
EFHC1	NR_033327.2		n.642+10A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFHC1	ENST00000371068.11	TSL:1 MANE Select	c.573+10A>G	intron	N/A	ENSP00000360107.4	Q5JVL4-1
EFHC1	ENST00000637340.1	TSL:1	n.1241+10A>G	intron	N/A
EFHC1	ENST00000637353.1	TSL:5	c.573+10A>G	intron	N/A	ENSP00000490441.1	A0A1B0GVB0

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28979

AN:

151994

Hom.:

3229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.237

AC:

59332

AN:

250182

AF XY:

0.232

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.208

AC:

303681

AN:

1461028

Hom.:

34176

Cov.:

AF XY:

0.209

AC XY:

151789

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.115

AC:

3835

AN:

33460

American (AMR)

AF:

0.453

AC:

20233

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5345

AN:

26126

East Asian (EAS)

AF:

0.253

AC:

10061

AN:

39690

South Asian (SAS)

AF:

0.263

AC:

22703

AN:

86220

European-Finnish (FIN)

AF:

0.192

AC:

10268

AN:

53382

Middle Eastern (MID)

AF:

0.181

AC:

1044

AN:

5764

European-Non Finnish (NFE)

AF:

0.196

AC:

217888

AN:

1111356

Other (OTH)

AF:

0.204

AC:

12304

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11421

22842

34263

45684

57105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7788

15576

23364

31152

38940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.191

AC:

29000

AN:

152114

Hom.:

3237

Cov.:

AF XY:

0.195

AC XY:

14535

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.118

AC:

4919

AN:

41514

American (AMR)

AF:

0.336

AC:

5124

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1119

AN:

5178

South Asian (SAS)

AF:

0.246

AC:

1186

AN:

4818

European-Finnish (FIN)

AF:

0.191

AC:

2020

AN:

10580

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.196

AC:

13330

AN:

67988

Other (OTH)

AF:

0.178

AC:

377

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1182

2364

3545

4727

5909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

902

Bravo

AF:

0.200

Asia WGS

AF:

0.215

AC:

745

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Juvenile myoclonic epilepsy (2)

not provided (2)

not specified (2)

Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

0.19

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over