4-148813816-A-T

Variant names:

• chr4-148813816-A-T
• rs1403454
• ENST00000661928.1:n.223-52941A>T

Variant summary

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

The ENST00000661928.1(ENSG00000287292):​n.223-52941A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,874 control chromosomes in the GnomAD database, including 2,833 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 0.16 (2833 hom., cov: 32)
• Consequence: ENSG00000287292 ENST00000661928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 7 publications found

Genes affected

ENSG00000287292 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377481	XR_001741437.2	n.285+6476T>A		intron_variant	Intron 4 of 12
LOC107986195	XR_001741441.2	n.3662-52941A>T		intron_variant	Intron 2 of 3
LOC105377481	XR_007058322.1	n.516+6476T>A		intron_variant	Intron 6 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287292	ENST00000661928.1	n.223-52941A>T		intron_variant	Intron 2 of 3
ENSG00000301224	ENST00000777100.1	n.461-8643T>A		intron_variant	Intron 2 of 6
ENSG00000301224	ENST00000777101.1	n.424+6476T>A		intron_variant	Intron 5 of 8
ENSG00000301224	ENST00000777102.1	n.254+6476T>A		intron_variant	Intron 3 of 7

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23601 AN: 151756 Hom.: 2833 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.155 AC: 23603 AN: 151874 Hom.: 2833 Cov.: 32 AF XY: 0.161 AC XY: 11957 AN XY: 74248

African (AFR) AF: 0.0515 AC: 2137 AN: 41520

American (AMR) AF: 0.356 AC: 5403 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 594 AN: 3460

East Asian (EAS) AF: 0.493 AC: 2544 AN: 5158

South Asian (SAS) AF: 0.176 AC: 846 AN: 4814

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10419 AN: 67822

Other (OTH) AF: 0.157 AC: 331 AN: 2106

Alfa AF: 0.151 Hom.: 275

Bravo AF: 0.176

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs1403454; hg19: chr4-149734968;