chr6-52419923-G-C

Position:

• chr6-52419923-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000635760.1(EFHC1):​c.-261-4023G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 353,162 control chromosomes in the GnomAD database, including 8,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3266 hom., cov: 32)
  • Exomes 𝑓: 0.21 (4954 hom.)
• Consequence: EFHC1 ENST00000635760.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

Genes affected

EFHC1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-52419923-G-C is Benign according to our data. Variant chr6-52419923-G-C is described in ClinVar as [Benign]. Clinvar id is 1266006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901331	XR_007059611.1	n.773+286C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000637340.1	n.181G>C		non_coding_transcript_exon_variant	1/10	1
EFHC1	ENST00000635760.1	c.-261-4023G>C		intron_variant		5		ENSP00000489765.1
EFHC1	ENST00000635984.1	c.-261-4023G>C		intron_variant		5		ENSP00000489921.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30475 AN: 152036 Hom.: 3267 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.214 AC: 43115 AN: 201008 Hom.: 4954 Cov.: 0 AF XY: 0.210 AC XY: 23105 AN XY: 110006

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.0552

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.200 AC: 30476 AN: 152154 Hom.: 3266 Cov.: 32 AF XY: 0.199 AC XY: 14782 AN XY: 74400

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0634

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.199

Alfa AF: 0.115 Hom.: 202

Bravo AF: 0.185

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs492153; hg19: chr6-52284721;