chr14-89932616-C-T

Variant names:

• chr14-89932616-C-T
• rs144958103
• NM_145231.4:c.229G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145231.4(EFCAB11):​c.229G>A​(p.Glu77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: EFCAB11 NM_145231.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.640
• Publications: 2 publications found

Genes affected

EFCAB11 (HGNC:20357): (EF-hand calcium binding domain 11) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259053 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011824906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145231.4. 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
	EFCAB11	NM_145231.4	MANE Select	c.229G>A	p.Glu77Lys	missense	Exon 4 of 6	NP_660274.1	Q9BUY7-1
	EFCAB11	NM_001284266.2		c.229G>A	p.Glu77Lys	missense	Exon 4 of 6	NP_001271195.1	Q9BUY7-5
	EFCAB11	NM_001284269.2		c.157G>A	p.Glu53Lys	missense	Exon 4 of 6	NP_001271198.1	Q9BUY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB11	ENST00000316738.12	TSL:2 MANE Select	c.229G>A	p.Glu77Lys	missense	Exon 4 of 6	ENSP00000326267.7	Q9BUY7-1
	EFCAB11	ENST00000555872.5	TSL:1	c.157G>A	p.Glu53Lys	missense	Exon 4 of 6	ENSP00000452320.1	Q9BUY7-2
	EFCAB11	ENST00000556005.1	TSL:1	c.157G>A	p.Glu53Lys	missense	Exon 4 of 6	ENSP00000452143.1	Q9BUY7-3

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 70 AN: 151984 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00167

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 250942 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000554 AC: 81 AN: 1460992 Hom.: 0 Cov.: 31 AF XY: 0.0000482 AC XY: 35 AN XY: 726852

African (AFR) AF: 0.00191 AC: 64 AN: 33446

American (AMR) AF: 0.000157 AC: 7 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39618

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111522

Other (OTH) AF: 0.0000994 AC: 6 AN: 60368

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74340

African (AFR) AF: 0.00166 AC: 69 AN: 41500

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.000631

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.64
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.021
Sift	Benign	0.24	T
Sift4G	Benign	0.28	T
Polyphen		0.022	B
Vest4		0.15
MVP		0.42
MPC		0.062
ClinPred		0.017	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.45
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs144958103; hg19: chr14-90398960;