rs4273712

Variant names:

• chr6-126643364-A-G
• rs4273712
• ENST00000650727.1:n.1167-21491T>C

Variant summary

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

The ENST00000650727.1(ENSG00000293110):​n.1167-21491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 399,210 control chromosomes in the GnomAD database, including 17,934 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 0.24 (5356 hom., cov: 32)
  • Exomes 𝑓: 0.30 (12578 hom.)
• Consequence: ENSG00000293110 ENST00000650727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 31 publications found

Genes affected

ENSG00000293110 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293110	ENST00000650727.1	n.1167-21491T>C		intron_variant	Intron 9 of 14
ENSG00000293110	ENST00000651326.1	n.694-39899T>C		intron_variant	Intron 3 of 6
ENSG00000293110	ENST00000652545.1	n.1477-21491T>C		intron_variant	Intron 10 of 15

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36841 AN: 152054 Hom.: 5354 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.305 AC: 75316 AN: 247038 Hom.: 12578 AF XY: 0.309 AC XY: 40156 AN XY: 130068

African (AFR) AF: 0.105 AC: 569 AN: 5412

American (AMR) AF: 0.471 AC: 4446 AN: 9440

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 2362 AN: 7272

East Asian (EAS) AF: 0.467 AC: 7501 AN: 16078

South Asian (SAS) AF: 0.381 AC: 9652 AN: 25354

European-Finnish (FIN) AF: 0.272 AC: 4326 AN: 15912

Middle Eastern (MID) AF: 0.345 AC: 379 AN: 1098

European-Non Finnish (NFE) AF: 0.274 AC: 41633 AN: 151702

Other (OTH) AF: 0.301 AC: 4448 AN: 14770

GnomAD4 genome AF: 0.242 AC: 36850 AN: 152172 Hom.: 5356 Cov.: 32 AF XY: 0.249 AC XY: 18545 AN XY: 74430

African (AFR) AF: 0.0878 AC: 3647 AN: 41546

American (AMR) AF: 0.388 AC: 5929 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2366 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4816

European-Finnish (FIN) AF: 0.275 AC: 2919 AN: 10606

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18233 AN: 67976

Other (OTH) AF: 0.282 AC: 593 AN: 2106

Alfa AF: 0.273 Hom.: 28214

Bravo AF: 0.250

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs4273712; hg19: chr6-126964510; COSMIC: COSV69095953;