16-31399864-C-T

Position:

• chr16-31399864-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ITGAD	NM_005353.3	c.427+1955C>T		intron_variant		ENST00000389202.3	NP_005344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAD	ENST00000389202.3	c.427+1955C>T		intron_variant		1	NM_005353.3	ENSP00000373854	P1
ITGAD	ENST00000444228.2	n.453+1955C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.569

Alfa AF: 0.544 Hom.: 28053

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

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: rs2454908; hg19: chr16-31411185;