6-52469350-C-T

Variant names:

• chr6-52469350-C-T
• rs115913738
• NM_018100.4:c.1155C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018100.4(EFHC1):​c.1155C>T​(p.Asn385Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,613,952 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: EFHC1 NM_018100.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0900
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-52469350-C-T is Benign according to our data. Variant chr6-52469350-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.09 with no splicing effect.
• BS2: High AC in GnomAd4 at 298 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	NM_018100.4	MANE Select	c.1155C>T	p.Asn385Asn	synonymous	Exon 7 of 11	NP_060570.2	Q5JVL4-1
	EFHC1	NM_001172420.2		c.1098C>T	p.Asn366Asn	synonymous	Exon 8 of 12	NP_001165891.1	Q5JVL4-3
	EFHC1	NR_033327.2		n.2481C>T		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	ENST00000371068.11	TSL:1 MANE Select	c.1155C>T	p.Asn385Asn	synonymous	Exon 7 of 11	ENSP00000360107.4	Q5JVL4-1
	EFHC1	ENST00000637340.1	TSL:1	n.3080C>T		non_coding_transcript_exon	Exon 6 of 10
	EFHC1	ENST00000637353.1	TSL:5	c.1155C>T	p.Asn385Asn	synonymous	Exon 7 of 11	ENSP00000490441.1	A0A1B0GVB0

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 296 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00668

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000557 AC: 140 AN: 251334 AF XY: 0.000412

Gnomad AFR exome AF: 0.00726

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000226 AC: 331 AN: 1461680 Hom.: 1 Cov.: 30 AF XY: 0.000190 AC XY: 138 AN XY: 727136

African (AFR) AF: 0.00738 AC: 247 AN: 33476

American (AMR) AF: 0.000559 AC: 25 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111896

Other (OTH) AF: 0.000679 AC: 41 AN: 60386

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00200 AC XY: 149 AN XY: 74464

African (AFR) AF: 0.00671 AC: 279 AN: 41560

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000717 Hom.: 0

Bravo AF: 0.00227

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		0.090
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs115913738; hg19: chr6-52334148;