rs2664588

Variant names:

• chr20-47951890-C-T
• rs2664588
• ENST00000431915.1:n.260C>T

Variant summary

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

The ENST00000431915.1(ENSG00000234967):​n.260C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,166 control chromosomes in the GnomAD database, including 11,031 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 0.35 (11030 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: ENSG00000234967 ENST00000431915.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 5 publications found

Genes affected

ENSG00000234967 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000431915.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000234967	ENST00000431915.1	TSL:2	n.260C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000234967	ENST00000666669.1		n.262C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000234967	ENST00000416646.2	TSL:2	n.140+45C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52705 AN: 151942 Hom.: 11035 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.208 AC: 22 AN: 106 Hom.: 1 Cov.: 0 AF XY: 0.197 AC XY: 13 AN XY: 66

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.156 AC: 14 AN: 90

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 6 AN: 12

Other (OTH) AF: 0.500 AC: 2 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00111084), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.347 AC: 52699 AN: 152060 Hom.: 11030 Cov.: 32 AF XY: 0.349 AC XY: 25959 AN XY: 74324

African (AFR) AF: 0.112 AC: 4646 AN: 41482

American (AMR) AF: 0.452 AC: 6910 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3466

East Asian (EAS) AF: 0.109 AC: 565 AN: 5172

South Asian (SAS) AF: 0.388 AC: 1874 AN: 4824

European-Finnish (FIN) AF: 0.506 AC: 5349 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30292 AN: 67952

Other (OTH) AF: 0.364 AC: 769 AN: 2110

Alfa AF: 0.427 Hom.: 12562

Bravo AF: 0.332

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.35
PhyloP100		-2.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2664588;

hg19: chr20-46580634;