rs983271

Positions:

• chr8-35557134-T-C
• chr8-35557134-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
UNC5D	NM_080872.4	c.322+7624T>C		intron_variant		ENST00000404895.7	NP_543148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5D	ENST00000404895.7	c.322+7624T>C		intron_variant		1	NM_080872.4	ENSP00000385143	P4

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

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.213

Alfa AF: 0.139 Hom.: 1030

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

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: rs983271; hg19: chr8-35414652;