rs745721550

Variant names:

• chr3-105520057-TCCCC-T
• rs745721550
• NM_001627.4:c.74-8_74-5delCCCC

Your query was ambiguous. Multiple possible variants found:

• chr3-105520057-TCCCC-T
• chr3-105520057-TCCCC-TCCC
• chr3-105520057-TCCCC-TCCCCC
• chr3-105520057-TCCCC-TCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001627.4(ALCAM):​c.74-8_74-5delCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,304 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ALCAM NM_001627.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.74-8_74-5delCCCC		splice_region_variant, intron_variant	Intron 1 of 15	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.74-8_74-5delCCCC		splice_region_variant, intron_variant	Intron 1 of 14		NP_001230209.1
ALCAM	NM_001243281.2	c.74-8_74-5delCCCC		splice_region_variant, intron_variant	Intron 1 of 13		NP_001230210.1
ALCAM	NM_001243283.2	c.74-8_74-5delCCCC		splice_region_variant, intron_variant	Intron 1 of 2		NP_001230212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.74-9_74-6delCCCC		splice_region_variant, intron_variant	Intron 1 of 15	1	NM_001627.4	ENSP00000305988.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1317304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 655372

⚠️ 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: 28536

American (AMR) AF: 0.0000299 AC: 1 AN: 33410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23282

East Asian (EAS) AF: 0.00 AC: 0 AN: 37276

South Asian (SAS) AF: 0.00 AC: 0 AN: 72336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1011402

Other (OTH) AF: 0.00 AC: 0 AN: 54542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), 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
PhyloP100		0.21

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: rs745721550; hg19: chr3-105238901;