rs2765501

Positions:

• chr1-157834858-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005894.3(CD5L):​c.377-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 740,606 control chromosomes in the GnomAD database, including 56,104 homozygotes. 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: 𝑓 0.31 (9248 hom., cov: 32)
  • Exomes 𝑓: 0.39 (46856 hom.)
• Consequence: CD5L NM_005894.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD5L	NM_005894.3	c.377-110C>T		intron_variant		ENST00000368174.5
CD5L	NM_001347698.2	c.377-110C>T		intron_variant
CD5L	XM_017002806.2	c.377-110C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD5L	ENST00000368174.5	c.377-110C>T		intron_variant		1	NM_005894.3	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46817 AN: 151988 Hom.: 9245 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.387 AC: 228017 AN: 588500 Hom.: 46856 AF XY: 0.387 AC XY: 117667 AN XY: 303924

Gnomad4 AFR exome AF: 0.0661

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.308 AC: 46818 AN: 152106 Hom.: 9248 Cov.: 32 AF XY: 0.313 AC XY: 23300 AN XY: 74356

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.308

Alfa AF: 0.389 Hom.: 23975

Bravo AF: 0.275

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.074
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs2765501; hg19: chr1-157804648;