rs2241743

Variant names:

• chr4-95170373-G-A
• rs2241743
• NM_003728.4:c.2452-41C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-95170373-G-A
• chr4-95170373-G-C

Variant summary

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

The NM_003728.4(UNC5C):​c.2452-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,596,656 control chromosomes in the GnomAD database, including 253,923 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 0.56 (24194 hom., cov: 33)
  • Exomes 𝑓: 0.56 (229729 hom.)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.2452-41C>T		intron_variant	Intron 14 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.2509-41C>T		intron_variant	Intron 15 of 16		XP_005263378.1
UNC5C	XM_047416345.1	c.1408-41C>T		intron_variant	Intron 16 of 17		XP_047272301.1
UNC5C	XM_047416346.1	c.1408-41C>T		intron_variant	Intron 17 of 18		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.2452-41C>T		intron_variant	Intron 14 of 15	1	NM_003728.4	ENSP00000406022.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85190 AN: 151924 Hom.: 24168 Cov.: 33

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.554 AC: 135578 AN: 244652 AF XY: 0.543

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.667

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.560 AC: 808573 AN: 1444614 Hom.: 229729 Cov.: 31 AF XY: 0.554 AC XY: 396492 AN XY: 715630

African (AFR) AF: 0.551 AC: 18281 AN: 33166

American (AMR) AF: 0.692 AC: 30503 AN: 44094

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 16795 AN: 25406

East Asian (EAS) AF: 0.357 AC: 14036 AN: 39302

South Asian (SAS) AF: 0.371 AC: 31551 AN: 84966

European-Finnish (FIN) AF: 0.599 AC: 31789 AN: 53042

Middle Eastern (MID) AF: 0.626 AC: 3559 AN: 5684

European-Non Finnish (NFE) AF: 0.572 AC: 628778 AN: 1099350

Other (OTH) AF: 0.558 AC: 33281 AN: 59604

GnomAD4 genome AF: 0.561 AC: 85267 AN: 152042 Hom.: 24194 Cov.: 33 AF XY: 0.559 AC XY: 41555 AN XY: 74298

African (AFR) AF: 0.546 AC: 22650 AN: 41458

American (AMR) AF: 0.642 AC: 9818 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2288 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1849 AN: 5156

South Asian (SAS) AF: 0.354 AC: 1707 AN: 4818

European-Finnish (FIN) AF: 0.609 AC: 6437 AN: 10568

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38656 AN: 67970

Other (OTH) AF: 0.572 AC: 1206 AN: 2108

Alfa AF: 0.564 Hom.: 42615

Bravo AF: 0.569

Asia WGS AF: 0.372 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.55
PhyloP100		-0.033
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: rs2241743; hg19: chr4-96091524; COSMIC: COSV71660260;