rs4577954

chr8-35461963-G-Achr8-35461963-G-Cchr8-35461963-G-T

Variant summary

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

The NM_080872.4(UNC5D):c.104-87329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,124 control chromosomes in the GnomAD database, including 54,551 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 0.84 (54551 hom., cov: 32)
• Consequence: UNC5D NM_080872.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5D	NM_080872.4	c.104-87329G>A		intron_variant		ENST00000404895.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5D	ENST00000404895.7	c.104-87329G>A		intron_variant		1	NM_080872.4	P4
UNC5D	ENST00000287272.6	c.104-87329G>A		intron_variant		5
UNC5D	ENST00000416672.5	c.104-87329G>A		intron_variant		5		A1
UNC5D	ENST00000420357.5	c.104-87329G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128124 AN: 152006 Hom.: 54529 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.843 AC: 128196 AN: 152124 Hom.: 54551 Cov.: 32 AF XY: 0.842 AC XY: 62614 AN XY: 74380

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.849

Alfa AF: 0.891 Hom.: 78781

Bravo AF: 0.826

Asia WGS AF: 0.790 AC: 2746 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.2
Dann	Benign	0.73

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: rs4577954; hg19: chr8-35319481; COSMIC: COSV54807947;