rs2118922

Positions:

• chr4-177245920-G-A

Variant summary

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

The ENST00000512516.1(ENSG00000249008):​n.256+108C>T 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 0.492 in 186,906 control chromosomes in the GnomAD database, including 22,814 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 0.49 (18628 hom., cov: 34)
  • Exomes 𝑓: 0.49 (4186 hom.)
• Consequence: ENST00000512516.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377557	XR_001741925.2	n.235-25245C>T		intron_variant, non_coding_transcript_variant
LOC105377557	XR_007058380.1	n.235-25245C>T		intron_variant, non_coding_transcript_variant
LOC105377557	XR_007058381.1	n.1902+24943C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000512516.1	n.256+108C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000656694.1	n.113-25245C>T		intron_variant, non_coding_transcript_variant
	ENST00000662794.1	n.185+24943C>T		intron_variant, non_coding_transcript_variant
	ENST00000667713.1	n.208-25245C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74926 AN: 151894 Hom.: 18614 Cov.: 34

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.488 AC: 17035 AN: 34894 Hom.: 4186 AF XY: 0.480 AC XY: 9630 AN XY: 20050

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.493 AC: 74990 AN: 152012 Hom.: 18628 Cov.: 34 AF XY: 0.492 AC XY: 36580 AN XY: 74288

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.535

Alfa AF: 0.509 Hom.: 45986

Bravo AF: 0.488

Asia WGS AF: 0.470 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
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: rs2118922; hg19: chr4-178167074;