chr3-105367241-C-T

Position:

• chr3-105367241-C-T

Variant summary

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

The NM_001627.4(ALCAM):​c.-168C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 623,554 control chromosomes in the GnomAD database, including 3,010 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 0.097 (791 hom., cov: 31)
  • Exomes 𝑓: 0.090 (2219 hom.)
• Consequence: ALCAM NM_001627.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.-168C>T		5_prime_UTR_variant	1/16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.-168C>T		5_prime_UTR_variant	1/15		NP_001230209.1
ALCAM	NM_001243281.2	c.-168C>T		5_prime_UTR_variant	1/14		NP_001230210.1
ALCAM	NM_001243283.2	c.-168C>T		5_prime_UTR_variant	1/3		NP_001230212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.-168C>T		5_prime_UTR_variant	1/16	1	NM_001627.4	ENSP00000305988	A1
ALCAM	ENST00000470756.5	n.324C>T		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14749 AN: 151790 Hom.: 788 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0855

GnomAD4 exome AF: 0.0903 AC: 42577 AN: 471646 Hom.: 2219 Cov.: 6 AF XY: 0.0930 AC XY: 23054 AN XY: 247794

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0574

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0726

Gnomad4 OTH exome AF: 0.0851

GnomAD4 genome AF: 0.0971 AC: 14754 AN: 151908 Hom.: 791 Cov.: 31 AF XY: 0.0989 AC XY: 7341 AN XY: 74224

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0780 Hom.: 286

Bravo AF: 0.0945

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6437585; hg19: chr3-105086085;