6-52420216-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000637340.1(EFHC1):n.474A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 758,872 control chromosomes in the GnomAD database, including 890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (243 hom., cov: 32)
  • Exomes 𝑓: 0.026 (647 hom.)
• Consequence: EFHC1 ENST00000637340.1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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]

LOC124901331 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-52420216-A-G is Benign according to our data. Variant chr6-52420216-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 357475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901331	XR_007059611.1	n.766T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHC1	ENST00000637340.1	n.474A>G		non_coding_transcript_exon_variant	1/10	1
EFHC1	ENST00000636489.1	c.-380A>G		5_prime_UTR_variant	1/12	5
EFHC1	ENST00000635760.1	c.-261-3730A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6585 AN: 152188 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0290 AC: 4108 AN: 141872 Hom.: 188 AF XY: 0.0271 AC XY: 2059 AN XY: 76070

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.00203

Gnomad EAS exome AF: 0.150

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0188

GnomAD4 exome AF: 0.0265 AC: 16065 AN: 606566 Hom.: 647 Cov.: 7 AF XY: 0.0252 AC XY: 8171 AN XY: 324886

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.00178

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.0376

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0434 AC: 6603 AN: 152306 Hom.: 243 Cov.: 32 AF XY: 0.0439 AC XY: 3271 AN XY: 74474

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0187 Hom.: 51

Bravo AF: 0.0434

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Juvenile myoclonic epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	3.8
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296196; hg19: chr6-52285014; COSMIC: COSV64136120; COSMIC: COSV64136120;