chr8-35557134-T-C

Variant names:

• chr8-35557134-T-C
• rs983271
• NM_080872.4:c.322+7624T>C

Variant summary

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

The NM_080872.4(UNC5D):​c.322+7624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,092 control chromosomes in the GnomAD database, including 6,108 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 0.23 (6108 hom., cov: 32)
• Consequence: UNC5D NM_080872.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 4 publications found

Genes affected

UNC5D (HGNC:18634): (unc-5 netrin receptor D) Predicted to enable netrin receptor activity. Involved in cell-cell adhesion via plasma-membrane adhesion molecules. Predicted to be located in cell surface and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5D	NM_080872.4	c.322+7624T>C		intron_variant	Intron 2 of 16	ENST00000404895.7	NP_543148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5D	ENST00000404895.7	c.322+7624T>C		intron_variant	Intron 2 of 16	1	NM_080872.4	ENSP00000385143.2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34623 AN: 151974 Hom.: 6072 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.228 AC: 34711 AN: 152092 Hom.: 6108 Cov.: 32 AF XY: 0.227 AC XY: 16847 AN XY: 74370

African (AFR) AF: 0.479 AC: 19846 AN: 41438

American (AMR) AF: 0.278 AC: 4248 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1366 AN: 5150

South Asian (SAS) AF: 0.200 AC: 965 AN: 4824

European-Finnish (FIN) AF: 0.0533 AC: 566 AN: 10622

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0975 AC: 6631 AN: 68000

Other (OTH) AF: 0.213 AC: 448 AN: 2106

Alfa AF: 0.140 Hom.: 1196

Bravo AF: 0.255

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.59
PhyloP100		-0.23
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: rs983271; hg19: chr8-35414652;