12-4991081-G-T

Variant names:

• chr12-4991081-G-T
• rs1014665
• ENST00000638821.1:n.573-19069G>T

Variant summary

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

The ENST00000638821.1(ENSG00000256654):​n.573-19069G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,996 control chromosomes in the GnomAD database, including 16,176 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 0.46 (16176 hom., cov: 32)
• Consequence: ENSG00000256654 ENST00000638821.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 4 publications found

Genes affected

ENSG00000256654 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 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
ENSG00000256654	ENST00000638821.1	n.573-19069G>T		intron_variant	Intron 1 of 1	5
ENSG00000256654	ENST00000639005.1	n.684+9799G>T		intron_variant	Intron 2 of 5	5
ENSG00000256654	ENST00000640862.1	n.703+9799G>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69203 AN: 151878 Hom.: 16153 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.456 AC: 69282 AN: 151996 Hom.: 16176 Cov.: 32 AF XY: 0.453 AC XY: 33646 AN XY: 74270

African (AFR) AF: 0.394 AC: 16308 AN: 41436

American (AMR) AF: 0.345 AC: 5273 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1959 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2294 AN: 4814

European-Finnish (FIN) AF: 0.522 AC: 5504 AN: 10550

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34907 AN: 67976

Other (OTH) AF: 0.469 AC: 988 AN: 2106

Alfa AF: 0.479 Hom.: 17838

Bravo AF: 0.438

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.051
DANN	Benign	0.31
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1014665; hg19: chr12-5100247;