chr12-7357451-C-T

Variant names:

• chr12-7357451-C-T
• rs558582662
• NM_174941.6:c.4315G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174941.6(CD163L1):​c.4315G>A​(p.Asp1439Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,612,506 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 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: CD163L1 NM_174941.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0940
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027856797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174941.6. 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
	CD163L1	NM_174941.6	MANE Select	c.4315G>A	p.Asp1439Asn	missense	Exon 19 of 20	NP_777601.3	Q9NR16-1
	CD163L1	NM_001297650.2		c.4345G>A	p.Asp1449Asn	missense	Exon 19 of 20	NP_001284579.2	Q9NR16-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD163L1	ENST00000313599.8	TSL:1 MANE Select	c.4315G>A	p.Asp1439Asn	missense	Exon 19 of 20	ENSP00000315945.3	Q9NR16-1
	CD163L1	ENST00000416109.2	TSL:2	c.4345G>A	p.Asp1449Asn	missense	Exon 19 of 20	ENSP00000393474.2	Q9NR16-4
	CD163L1	ENST00000878199.1		c.4249G>A	p.Asp1417Asn	missense	Exon 18 of 19	ENSP00000548258.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152054 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000717 AC: 18 AN: 250970 AF XY: 0.0000811

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000872

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000657 AC: 96 AN: 1460452 Hom.: 0 Cov.: 30 AF XY: 0.0000743 AC XY: 54 AN XY: 726538

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.0000897 AC: 4 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 33 AN: 26066

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

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

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111090

Other (OTH) AF: 0.000133 AC: 8 AN: 60298

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152054 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.000263 AC: 4 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.078
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.2
DANN	Benign	0.30
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.00094	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.094
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.0090
Sift	Uncertain	0.012	D
Sift4G	Benign	0.11	T
Polyphen		0.10	B
Vest4		0.099
MutPred		0.42		Gain of catalytic residue at S1438 (P = 0)
MVP		0.28
MPC		0.22
ClinPred		0.019	T
GERP RS		-1.6
Varity_R		0.043
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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: rs558582662; hg19: chr12-7510047; COSMIC: COSV58013465;