6-52420101-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000637340.1(EFHC1):n.359A>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 0.00205 in 539,346 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (2 hom.)
• Consequence: EFHC1 ENST00000637340.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00900

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-52420101-A-G is Benign according to our data. Variant chr6-52420101-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1321733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00548 (834/152262) while in subpopulation AFR AF= 0.0189 (787/41566). AF 95% confidence interval is 0.0178. There are 8 homozygotes in gnomad4. There are 412 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 828 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901331	XR_007059611.1	n.773+108T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHC1	ENST00000637340.1	n.359A>G		non_coding_transcript_exon_variant	1/10	1
EFHC1	ENST00000635760.1	c.-261-3845A>G		intron_variant		5
EFHC1	ENST00000635984.1	c.-261-3845A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00544 AC: 828 AN: 152144 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.000708 AC: 274 AN: 387084 Hom.: 2 Cov.: 0 AF XY: 0.000610 AC XY: 127 AN XY: 208156

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.000902

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000625

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00548 AC: 834 AN: 152262 Hom.: 8 Cov.: 32 AF XY: 0.00553 AC XY: 412 AN XY: 74446

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00368 Hom.: 2

Bravo AF: 0.00567

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.1
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150082340; hg19: chr6-52284899;