rs2252459

Variant names:

• chr3-105527928-G-A
• rs2252459
• NM_001627.4:c.394+3420G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-105527928-G-A
• chr3-105527928-G-C
• chr3-105527928-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.394+3420G>A		intron_variant	Intron 3 of 15	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.394+3420G>A		intron_variant	Intron 3 of 14		NP_001230209.1
ALCAM	NM_001243281.2	c.394+3420G>A		intron_variant	Intron 3 of 13		NP_001230210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.394+3420G>A		intron_variant	Intron 3 of 15	1	NM_001627.4	ENSP00000305988.5
ALCAM	ENST00000472644.6	c.394+3420G>A		intron_variant	Intron 3 of 14	1		ENSP00000419236.2
ALCAM	ENST00000486979.6	c.241+3420G>A		intron_variant	Intron 3 of 15	5		ENSP00000418213.2
ALCAM	ENST00000481337.5	n.523+3420G>A		intron_variant	Intron 4 of 9	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

African (AFR) AF: 0.649 AC: 25689 AN: 39592

American (AMR) AF: 0.690 AC: 9933 AN: 14388

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2205 AN: 3340

East Asian (EAS) AF: 0.896 AC: 4416 AN: 4926

South Asian (SAS) AF: 0.670 AC: 3128 AN: 4666

European-Finnish (FIN) AF: 0.680 AC: 6834 AN: 10048

Middle Eastern (MID) AF: 0.606 AC: 171 AN: 282

European-Non Finnish (NFE) AF: 0.602 AC: 39710 AN: 65942

Other (OTH) AF: 0.643 AC: 1304 AN: 2028

Alfa AF: 0.654 Hom.: 16715

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
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs2252459; hg19: chr3-105246772;