12-7368162-G-T

Variant names:

• chr12-7368162-G-T
• NM_174941.6:c.4108C>A

Variant summary

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

The NM_174941.6(CD163L1):​c.4108C>A​(p.Leu1370Ile) 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. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD163L1 NM_174941.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48

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]

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=0.07750398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD163L1	NM_174941.6	c.4108C>A	p.Leu1370Ile	missense_variant	Exon 17 of 20	ENST00000313599.8	NP_777601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD163L1	ENST00000313599.8	c.4108C>A	p.Leu1370Ile	missense_variant	Exon 17 of 20	1	NM_174941.6	ENSP00000315945.3
CD163L1	ENST00000416109.2	c.4138C>A	p.Leu1380Ile	missense_variant	Exon 17 of 20	2		ENSP00000393474.2
CD163L1	ENST00000539726.5	c.73C>A	p.Leu25Ile	missense_variant	Exon 2 of 5	5		ENSP00000438217.1
CD163L1	ENST00000546182.1	n.73C>A		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000443004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458666 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4108C>A (p.L1370I) alteration is located in exon 17 (coding exon 17) of the CD163L1 gene. This alteration results from a C to A substitution at nucleotide position 4108, causing the leucine (L) at amino acid position 1370 to be replaced by an isoleucine (I). 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	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.7
DANN	Benign	0.96
DEOGEN2	Benign	0.0022	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.050
Sift	Benign	0.27	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.69	P;.
Vest4		0.11
MutPred		0.57		Gain of catalytic residue at L1372 (P = 0);.;
MVP		0.18
MPC		0.26
ClinPred		0.074	T
GERP RS		-2.7
Varity_R		0.038
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7520758;