chr12-7367263-C-G

Position:

• chr12-7367263-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174941.6(CD163L1):​c.4252G>C​(p.Glu1418Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD163L1 NM_174941.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10150987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD163L1	NM_174941.6	c.4252G>C	p.Glu1418Gln	missense_variant	18/20	ENST00000313599.8	NP_777601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD163L1	ENST00000313599.8	c.4252G>C	p.Glu1418Gln	missense_variant	18/20	1	NM_174941.6	ENSP00000315945.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2023

The c.4252G>C (p.E1418Q) alteration is located in exon 18 (coding exon 18) of the CD163L1 gene. This alteration results from a G to C substitution at nucleotide position 4252, causing the glutamic acid (E) at amino acid position 1418 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.088
Sift	Benign	0.035	D;D
Sift4G	Benign	0.099	T;T
Polyphen		0.99	D;.
Vest4		0.068
MutPred		0.25		Gain of catalytic residue at L1415 (P = 0.0022);.;
MVP		0.46
MPC		0.59
ClinPred		0.15	T
GERP RS		1.9
Varity_R		0.056
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7519859;