rs145367062

Variant names:

• chr6-52424092-A-G
• rs145367062
• NM_018100.4:c.210A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018100.4(EFHC1):​c.210A>G​(p.Pro70Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,614,190 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: EFHC1 NM_018100.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.614
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-52424092-A-G is Benign according to our data. Variant chr6-52424092-A-G is described in ClinVar as Benign. ClinVar VariationId is 137194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.614 with no splicing effect.
• BS2: High AC in GnomAd4 at 535 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	NM_018100.4	MANE Select	c.210A>G	p.Pro70Pro	synonymous	Exon 2 of 11	NP_060570.2	Q5JVL4-1
	EFHC1	NM_001172420.2		c.153A>G	p.Pro51Pro	synonymous	Exon 3 of 12	NP_001165891.1	Q5JVL4-3
	EFHC1	NR_033327.2		n.279A>G		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	ENST00000371068.11	TSL:1 MANE Select	c.210A>G	p.Pro70Pro	synonymous	Exon 2 of 11	ENSP00000360107.4	Q5JVL4-1
	EFHC1	ENST00000637340.1	TSL:1	n.878A>G		non_coding_transcript_exon	Exon 2 of 10
	EFHC1	ENST00000637353.1	TSL:5	c.210A>G	p.Pro70Pro	synonymous	Exon 2 of 11	ENSP00000490441.1	A0A1B0GVB0

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 530 AN: 152182 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00102 AC: 257 AN: 251476 AF XY: 0.000728

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000381 AC: 557 AN: 1461890 Hom.: 2 Cov.: 33 AF XY: 0.000338 AC XY: 246 AN XY: 727248

African (AFR) AF: 0.0125 AC: 420 AN: 33480

American (AMR) AF: 0.00116 AC: 52 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1112008

Other (OTH) AF: 0.00103 AC: 62 AN: 60396

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152300 Hom.: 3 Cov.: 32 AF XY: 0.00330 AC XY: 246 AN XY: 74486

African (AFR) AF: 0.0122 AC: 505 AN: 41550

American (AMR) AF: 0.00144 AC: 22 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00404

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.55
PhyloP100		-0.61
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism

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: rs145367062; hg19: chr6-52288890;