3-19918264-G-A

Variant names:

• chr3-19918264-G-A
• rs2929366
• NM_144715.4:c.1145C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144715.4(EFHB):​c.1145C>T​(p.Thr382Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,609,600 control chromosomes in the GnomAD database, including 352,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35988 hom., cov: 29)
  • Exomes 𝑓: 0.65 (316538 hom.)
• Consequence: EFHB NM_144715.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 35 publications found

Genes affected

EFHB (HGNC:26330): (EF-hand domain family member B) Enables calcium ion sensor activity. Involved in negative regulation of protein binding activity; regulation of calcineurin-NFAT signaling cascade; and regulation of store-operated calcium entry. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0044816E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHB	NM_144715.4	MANE Select	c.1145C>T	p.Thr382Ile	missense	Exon 4 of 13	NP_653316.3
	EFHB	NM_001330688.2		c.755C>T	p.Thr252Ile	missense	Exon 6 of 15	NP_001317617.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHB	ENST00000295824.14	TSL:1 MANE Select	c.1145C>T	p.Thr382Ile	missense	Exon 4 of 13	ENSP00000295824.9
	EFHB	ENST00000344838.8	TSL:2	c.755C>T	p.Thr252Ile	missense	Exon 6 of 15	ENSP00000342263.4
	EFHB	ENST00000440022.1	TSL:5	c.356C>T	p.Thr119Ile	missense	Exon 3 of 7	ENSP00000396778.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103199 AN: 151470 Hom.: 35951 Cov.: 29

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.614 AC: 152453 AN: 248340 AF XY: 0.622

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.327

Gnomad FIN exome AF: 0.688

Gnomad NFE exome AF: 0.668

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.653 AC: 952661 AN: 1458014 Hom.: 316538 Cov.: 48 AF XY: 0.653 AC XY: 473658 AN XY: 725170

African (AFR) AF: 0.808 AC: 26833 AN: 33198

American (AMR) AF: 0.423 AC: 18679 AN: 44146

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 17117 AN: 26034

East Asian (EAS) AF: 0.299 AC: 11868 AN: 39632

South Asian (SAS) AF: 0.649 AC: 55256 AN: 85150

European-Finnish (FIN) AF: 0.686 AC: 36567 AN: 53314

Middle Eastern (MID) AF: 0.623 AC: 3581 AN: 5748

European-Non Finnish (NFE) AF: 0.670 AC: 743533 AN: 1110564

Other (OTH) AF: 0.651 AC: 39227 AN: 60228

GnomAD4 genome AF: 0.681 AC: 103295 AN: 151586 Hom.: 35988 Cov.: 29 AF XY: 0.678 AC XY: 50244 AN XY: 74076

African (AFR) AF: 0.805 AC: 33270 AN: 41344

American (AMR) AF: 0.550 AC: 8378 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2265 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1684 AN: 5122

South Asian (SAS) AF: 0.638 AC: 3058 AN: 4792

European-Finnish (FIN) AF: 0.682 AC: 7130 AN: 10460

Middle Eastern (MID) AF: 0.617 AC: 179 AN: 290

European-Non Finnish (NFE) AF: 0.667 AC: 45279 AN: 67860

Other (OTH) AF: 0.644 AC: 1353 AN: 2100

Alfa AF: 0.666 Hom.: 85839

Bravo AF: 0.669

ESP6500AA AF: 0.805 AC: 3546

ESP6500EA AF: 0.666 AC: 5725

ExAC AF: 0.629 AC: 76422

Asia WGS AF: 0.491 AC: 1711 AN: 3478

EpiCase AF: 0.648

EpiControl AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.7
DANN	Benign	0.82
DEOGEN2	Benign	0.00010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.043	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.17
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.025
Sift	Benign	0.56	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.062
MPC		0.034
ClinPred		0.0095	T
GERP RS		1.6
Varity_R		0.019
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs2929366; hg19: chr3-19959756; COSMIC: COSV55546252;