rs10012227

Positions:

• chr4-18635692-G-A
• chr4-18635692-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652661.1(ENSG00000286046):​n.614+6397G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,164 control chromosomes in the GnomAD database, including 3,432 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 0.19 (3432 hom., cov: 32)
• Consequence: ENST00000652661.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374510	XR_001741602.2	n.286+6397G>A		intron_variant, non_coding_transcript_variant
LOC105374510	XR_001741601.2	n.1018+6397G>A		intron_variant, non_coding_transcript_variant
LOC105374510	XR_925445.3	n.628+6397G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000652661.1	n.614+6397G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28758 AN: 152044 Hom.: 3417 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.189 AC: 28788 AN: 152164 Hom.: 3432 Cov.: 32 AF XY: 0.194 AC XY: 14449 AN XY: 74388

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.179

Alfa AF: 0.181 Hom.: 1325

Bravo AF: 0.208

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10012227; hg19: chr4-18637315;