rs1157

Positions:

• chr3-105576617-G-A

Variant summary

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

The NM_001627.4(ALCAM):​c.*2166G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,124 control chromosomes in the GnomAD database, including 2,418 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 0.16 (2412 hom., cov: 32)
  • Exomes 𝑓: 0.21 (6 hom.)
• Consequence: ALCAM NM_001627.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

ALCAM (HGNC:400): (activated leukocyte cell adhesion molecule) This gene encodes activated leukocyte cell adhesion molecule (ALCAM), also known as CD166 (cluster of differentiation 166), which is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain. This protein binds to T-cell differentiation antigene CD6, and is implicated in the processes of cell adhesion and migration. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.*2166G>A		3_prime_UTR_variant	16/16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.*2166G>A		3_prime_UTR_variant	15/15		NP_001230209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.*2166G>A		3_prime_UTR_variant	16/16	1	NM_001627.4	ENSP00000305988.5
ALCAM	ENST00000472644.6	c.*2166G>A		3_prime_UTR_variant	15/15	1		ENSP00000419236.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24384 AN: 151682 Hom.: 2410 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.208 AC: 67 AN: 322 Hom.: 6 Cov.: 0 AF XY: 0.173 AC XY: 34 AN XY: 196

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.161 AC: 24376 AN: 151802 Hom.: 2412 Cov.: 32 AF XY: 0.163 AC XY: 12079 AN XY: 74156

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.170

Alfa AF: 0.195 Hom.: 5111

Bravo AF: 0.153

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.68

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: rs1157; hg19: chr3-105295461;