16-31399864-C-T

Variant names:

• chr16-31399864-C-T
• rs2454908
• NM_005353.3:c.427+1955C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005353.3(ITGAD):​c.427+1955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,004 control chromosomes in the GnomAD database, including 31,365 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 0.63 (31365 hom., cov: 31)
• Consequence: ITGAD NM_005353.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 10 publications found

Genes affected

ITGAD (HGNC:6146): (integrin subunit alpha D) This gene belongs to the beta-2 integrin family of membrane glycoproteins, which are are composed of non-covalently linked alpha and beta subunits to form a heterodimer. It encodes the alpha subunit of the cell surface heterodimers and is involved in the activation and adhesion functions of leukocytes. The gene is located about 11kb downstream of the integrin subunit alpha X gene, another member of the integrin family. It is expressed in the tissue and circulating myeloid leukocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ENSG00000308290 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAD	NM_005353.3	c.427+1955C>T		intron_variant	Intron 5 of 29	ENST00000389202.3	NP_005344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAD	ENST00000389202.3	c.427+1955C>T		intron_variant	Intron 5 of 29	1	NM_005353.3	ENSP00000373854.2
ITGAD	ENST00000444228.2	n.453+1955C>T		intron_variant	Intron 5 of 8	2
ENSG00000308290	ENST00000833001.1	n.453+4389G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95356 AN: 151884 Hom.: 31298 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.628 AC: 95485 AN: 152004 Hom.: 31365 Cov.: 31 AF XY: 0.628 AC XY: 46642 AN XY: 74290

African (AFR) AF: 0.814 AC: 33781 AN: 41476

American (AMR) AF: 0.523 AC: 7980 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3954 AN: 5160

South Asian (SAS) AF: 0.795 AC: 3824 AN: 4808

European-Finnish (FIN) AF: 0.526 AC: 5551 AN: 10554

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36731 AN: 67960

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.565 Hom.: 72426

Bravo AF: 0.631

Asia WGS AF: 0.774 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-1.1
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: rs2454908; hg19: chr16-31411185;