Genetic Variant EFCAB5:c.42+1G>A (chr17-29941839-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_198529.4(EFCAB5):c.42+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00393 in 1,602,532 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 64 hom. )

Consequence

EFCAB5
NM_198529.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 4.02

Publications

4 publications found

Variant links:

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 17-29941839-G-A is Benign according to our data. Variant chr17-29941839-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 585108.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198529.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFCAB5	NM_198529.4	MANE Select	c.42+1G>A	splice_donor intron	N/A	NP_940931.3	A4FU69-1
EFCAB5	NM_001145053.2		c.-126-401G>A	intron	N/A	NP_001138525.2	A4FU69-5
EFCAB5	NR_026738.2		n.205+1G>A	splice_donor intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.42+1G>A	splice_donor intron	N/A	ENSP00000378312.3	A4FU69-1
EFCAB5	ENST00000440741.7	TSL:1	n.42+1G>A	splice_donor intron	N/A	ENSP00000393095.2	A4FU69-2
EFCAB5	ENST00000536908.6	TSL:2	c.-126-401G>A	intron	N/A	ENSP00000440619.2	A4FU69-5

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

804

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00833

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00527

AC:

1216

AN:

230648

AF XY:

0.00527

show subpopulations

Gnomad AFR exome

AF:

0.0000716

Gnomad AMR exome

AF:

0.000853

Gnomad ASJ exome

AF:

0.00567

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.00679

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00378

AC:

5486

AN:

1450290

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

2866

AN XY:

720196

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33276

American (AMR)

AF:

0.000874

AC:

AN:

43458

Ashkenazi Jewish (ASJ)

AF:

0.00707

AC:

182

AN:

25756

East Asian (EAS)

AF:

0.00

AC:

AN:

39480

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84152

European-Finnish (FIN)

AF:

0.0176

AC:

929

AN:

52810

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00372

AC:

4110

AN:

1105648

Other (OTH)

AF:

0.00364

AC:

218

AN:

59952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

234

469

703

938

1172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.00528

AC:

804

AN:

152242

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41534

American (AMR)

AF:

0.000392

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00834

AC:

567

AN:

68020

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00629

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.00608

AC:

ExAC

AF:

0.00481

AC:

580

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Benign

0.96

Eigen

Pathogenic

0.88

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.85

PhyloP100

4.0

GERP RS

4.1

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.31

Position offset: -1

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

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