Variant 12-7369636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174941.6(CD163L1):c.3760G>A(p.Glu1254Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CD163L1
NM_174941.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.850

Variant links:

Genes affected

CD163L1 (HGNC:30375): (CD163 molecule like 1) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. The SRCR family is defined by a 100-110 amino acid SRCR domain, which may mediate protein-protein interaction and ligand binding. The encoded protein contains twelve SRCR domains, a transmembrane region and a cytoplasmic domain. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

CD163L1 links:

CD163L1 (HGNC:):

CD163L1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009443253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163L1	NM_174941.6 linkuse as main transcript	c.3760G>A	p.Glu1254Lys	missense_variant	15/20	ENST00000313599.8	NP_777601.3	Q9NR16-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD163L1	ENST00000313599.8 linkuse as main transcript	c.3760G>A	p.Glu1254Lys	missense_variant	15/20	1	NM_174941.6	ENSP00000315945.3		Q9NR16-1
CD163L1	ENST00000416109.2 linkuse as main transcript	c.3790G>A	p.Glu1264Lys	missense_variant	15/20	2		ENSP00000393474.2		Q9NR16-4

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250680

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000239

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1461784

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000486

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2023

The c.3760G>A (p.E1254K) alteration is located in exon 15 (coding exon 15) of the CD163L1 gene. This alteration results from a G to A substitution at nucleotide position 3760, causing the glutamic acid (E) at amino acid position 1254 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.1

DANN

Benign

0.76

DEOGEN2

Benign

0.00039

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.0040

Sift

Benign

0.39

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.20

B;.

Vest4

0.10

MVP

0.21

MPC

0.25

ClinPred

0.0013

GERP RS

-6.7

Varity_R

0.026

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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