chr1-157834858-G-T

Variant names:

• chr1-157834858-G-T
• rs2765501
• NM_005894.3:c.377-110C>A

Variant summary

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

The NM_005894.3(CD5L):​c.377-110C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000339 in 589,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CD5L NM_005894.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 0 publications found

Genes affected

CD5L (HGNC:1690): (CD5 molecule like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Predicted to act upstream of or within positive regulation of complement-dependent cytotoxicity and regulation of complement activation. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD5L	NM_005894.3	c.377-110C>A		intron_variant	Intron 3 of 5	ENST00000368174.5	NP_005885.1
CD5L	NM_001347698.2	c.377-110C>A		intron_variant	Intron 3 of 5		NP_001334627.1
CD5L	XM_017002806.2	c.377-110C>A		intron_variant	Intron 3 of 5		XP_016858295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD5L	ENST00000368174.5	c.377-110C>A		intron_variant	Intron 3 of 5	1	NM_005894.3	ENSP00000357156.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000339 AC: 2 AN: 589500 Hom.: 0 AF XY: 0.00000657 AC XY: 2 AN XY: 304450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15636

American (AMR) AF: 0.00 AC: 0 AN: 21194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14816

East Asian (EAS) AF: 0.00 AC: 0 AN: 32328

South Asian (SAS) AF: 0.00 AC: 0 AN: 49812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2418

European-Non Finnish (NFE) AF: 0.00000519 AC: 2 AN: 385190

Other (OTH) AF: 0.00 AC: 0 AN: 30628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.49
PhyloP100		-0.74

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

Other links and lift over

dbSNP: rs2765501; hg19: chr1-157804648;