rs10517128

Variant names:

• chr4-27779759-G-C
• rs10517128
• ENST00000849360.1:n.172-7565G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000849360.1(ENSG00000310375):​n.172-7565G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 152,258 control chromosomes in the GnomAD database, including 27 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 0.019 (27 hom., cov: 32)
• Consequence: ENSG00000310375 ENST00000849360.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 0 publications found

Genes affected

ENSG00000310375 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0191 (2903/152258) while in subpopulation NFE AF = 0.0219 (1493/68024). AF 95% confidence interval is 0.021. There are 27 homozygotes in GnomAd4. There are 1391 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 gene

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
ENSG00000310375	ENST00000849360.1	n.172-7565G>C		intron_variant	Intron 2 of 3
ENSG00000310375	ENST00000849361.1	n.396+537G>C		intron_variant	Intron 4 of 5
ENSG00000310375	ENST00000849362.1	n.203+537G>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2903 AN: 152140 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0191 AC: 2903 AN: 152258 Hom.: 27 Cov.: 32 AF XY: 0.0187 AC XY: 1391 AN XY: 74436

African (AFR) AF: 0.0174 AC: 722 AN: 41534

American (AMR) AF: 0.0206 AC: 315 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4824

European-Finnish (FIN) AF: 0.00782 AC: 83 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1493 AN: 68024

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0224 Hom.: 4

Bravo AF: 0.0204

Asia WGS AF: 0.00635 AC: 22 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	3.3
DANN	Benign	0.42
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs10517128; hg19: chr4-27781381;