rs509946

Variant names:

• chr6-52439192-G-A
• rs509946
• NM_018100.4:c.573+601G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-52439192-G-A
• chr6-52439192-G-C
• chr6-52439192-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018100.4(EFHC1):​c.573+601G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,906 control chromosomes in the GnomAD database, including 31,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31611 hom., cov: 32)
• Consequence: EFHC1 NM_018100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.573+601G>A		intron_variant	Intron 3 of 10	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.516+601G>A		intron_variant	Intron 4 of 11		NP_001165891.1
EFHC1	NR_033327.2	n.642+601G>A		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.573+601G>A		intron_variant	Intron 3 of 10	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96286 AN: 151788 Hom.: 31571 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 96372 AN: 151906 Hom.: 31611 Cov.: 32 AF XY: 0.637 AC XY: 47294 AN XY: 74252

African (AFR) AF: 0.778 AC: 32247 AN: 41454

American (AMR) AF: 0.696 AC: 10616 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4491 AN: 5190

South Asian (SAS) AF: 0.651 AC: 3129 AN: 4808

European-Finnish (FIN) AF: 0.468 AC: 4924 AN: 10528

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.542 AC: 36794 AN: 67902

Other (OTH) AF: 0.629 AC: 1327 AN: 2110

Alfa AF: 0.557 Hom.: 5095

Bravo AF: 0.660

Asia WGS AF: 0.696 AC: 2411 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.46
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs509946; hg19: chr6-52303990;