Variant rs775583843 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

The ENST00000371068.11(EFHC1):c.1841_1851+13del variant causes a splice donor, splice donor 5th base, coding sequence, intron change. The variant allele was found at a frequency of 0.0000675 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

EFHC1
ENST00000371068.11 splice_donor, splice_donor_5th_base, coding_sequence, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.70

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates 0.0431617264690588 fraction of the geneNo cryptic splice site detected. Exon removal results in frameshift change.

BP6

Variant 6-52490338-CTTGGTTAAGGAGGTCAGTATGAAT-C is Benign according to our data. Variant chr6-52490338-CTTGGTTAAGGAGGTCAGTATGAAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 411576.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
EFHC1	NM_018100.4 linkuse as main transcript	c.1841_1851+13del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	10/11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2 linkuse as main transcript	c.1784_1794+13del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/12		NP_001165891.1
EFHC1	NR_033327.2 linkuse as main transcript	n.3167_3177+13del	splice_donor_variant, splice_donor_5th_base_variant, non_coding_transcript_exon_variant, intron_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 linkuse as main transcript	c.1841_1851+13del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	10/11	1	NM_018100.4	ENSP00000360107	P1	Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000917

AC:

AN:

250924

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000670

AC:

AN:

1461686

Hom.:

AF XY:

0.0000633

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.0000729

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over