4-174524086-A-G

Variant names:

• chr4-174524086-A-G
• rs3756273
• ENST00000515178.1:n.1817T>C

Variant summary

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

The ENST00000515178.1(ENSG00000293043):​n.1817T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,150 control chromosomes in the GnomAD database, including 17,691 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 0.47 (17683 hom., cov: 32)
  • Exomes 𝑓: 0.54 (8 hom.)
• Consequence: ENSG00000293043 ENST00000515178.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 5 publications found

Genes affected

ENSG00000293043 (HGNC:):

ENSG00000251584 (HGNC:58913):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515178.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293043	ENST00000515178.1	TSL:1	n.1817T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000251584	ENST00000752455.1		n.21A>G		non_coding_transcript_exon	Exon 1 of 5
	ENSG00000251584	ENST00000752462.1		n.336A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71156 AN: 151986 Hom.: 17681 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.543 AC: 25 AN: 46 Hom.: 8 Cov.: 0 AF XY: 0.528 AC XY: 19 AN XY: 36

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 14 AN: 28

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.468 AC: 71181 AN: 152104 Hom.: 17683 Cov.: 32 AF XY: 0.466 AC XY: 34656 AN XY: 74338

African (AFR) AF: 0.302 AC: 12549 AN: 41524

American (AMR) AF: 0.491 AC: 7507 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1938 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3335 AN: 5166

South Asian (SAS) AF: 0.396 AC: 1913 AN: 4828

European-Finnish (FIN) AF: 0.498 AC: 5252 AN: 10554

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36985 AN: 67966

Other (OTH) AF: 0.500 AC: 1057 AN: 2114

Alfa AF: 0.521 Hom.: 10805

Bravo AF: 0.462

Asia WGS AF: 0.490 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.77
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3756273;

hg19: chr4-175445237;