4-95447154-A-T

Variant names:

• chr4-95447154-A-T
• rs7684538
• NM_003728.4:c.124+101580T>A

Variant summary

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

The NM_003728.4(UNC5C):​c.124+101580T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,170 control chromosomes in the GnomAD database, including 3,312 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 0.19 (3312 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 6 publications found

Genes affected

UNC5C (HGNC:12569): (unc-5 netrin receptor C) This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.124+101580T>A		intron_variant	Intron 1 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.124+101580T>A		intron_variant	Intron 1 of 16		XP_005263378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+101580T>A		intron_variant	Intron 1 of 15	1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.124+101580T>A		intron_variant	Intron 1 of 13	1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.124+101580T>A		intron_variant	Intron 1 of 10	1		ENSP00000426153.1
UNC5C	ENST00000504962.1	c.124+101580T>A		intron_variant	Intron 1 of 5	2		ENSP00000425117.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29444 AN: 152052 Hom.: 3313 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.193 AC: 29433 AN: 152170 Hom.: 3312 Cov.: 32 AF XY: 0.193 AC XY: 14333 AN XY: 74386

African (AFR) AF: 0.0988 AC: 4106 AN: 41546

American (AMR) AF: 0.196 AC: 2995 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.0858 AC: 444 AN: 5174

South Asian (SAS) AF: 0.108 AC: 521 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2634 AN: 10580

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17322 AN: 67988

Other (OTH) AF: 0.217 AC: 457 AN: 2106

Alfa AF: 0.137 Hom.: 279

Bravo AF: 0.190

Asia WGS AF: 0.0800 AC: 279 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.89
PhyloP100		0.28
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: rs7684538; hg19: chr4-96368305;