rs2252459

chr3-105527928-G-Achr3-105527928-G-Cchr3-105527928-G-T

Variant summary

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

The NM_001627.4(ALCAM):c.394+3420G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 146,090 control chromosomes in the GnomAD database, including 28,710 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 0.64 (28710 hom., cov: 26)
• Consequence: ALCAM NM_001627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALCAM	NM_001627.4	c.394+3420G>A		intron_variant		ENST00000306107.9
ALCAM	NM_001243280.2	c.394+3420G>A		intron_variant
ALCAM	NM_001243281.2	c.394+3420G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALCAM	ENST00000306107.9	c.394+3420G>A		intron_variant		1	NM_001627.4	A1
ALCAM	ENST00000472644.6	c.394+3420G>A		intron_variant		1		P3
ALCAM	ENST00000486979.6	c.241+3420G>A		intron_variant		5
ALCAM	ENST00000481337.5	n.523+3420G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 93914 AN: 145974 Hom.: 28674 Cov.: 26

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 94009 AN: 146090 Hom.: 28710 Cov.: 26 AF XY: 0.648 AC XY: 46127 AN XY: 71144

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.643

Alfa AF: 0.654 Hom.: 14918

Bravo AF: 0.697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.69
Dann	Benign	0.15

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: rs2252459; hg19: chr3-105246772;