chr21-44934140-A-G

Variant names:

• chr21-44934140-A-G
• rs9974172
• ENST00000615847.3:n.1986T>C

Variant summary

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

The ENST00000615847.3(LINC01547):​n.1986T>C 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 0.882 in 440,634 control chromosomes in the GnomAD database, including 171,802 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 0.90 (61324 hom., cov: 33)
  • Exomes 𝑓: 0.87 (110478 hom.)
• Consequence: LINC01547 ENST00000615847.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 8 publications found

Genes affected

LINC01547 (HGNC:15707): (long intergenic non-protein coding RNA 1547) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC01547	NR_027128.1	n.977T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC01547	ENST00000615847.3	n.1986T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
LINC01547	ENST00000397841.5	n.977T>C		non_coding_transcript_exon_variant	Exon 4 of 4	2
LINC01547	ENST00000654166.2	n.2154T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136393 AN: 152158 Hom.: 61263 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.875 AC: 252243 AN: 288358 Hom.: 110478 Cov.: 0 AF XY: 0.874 AC XY: 141035 AN XY: 161310

African (AFR) AF: 0.968 AC: 7698 AN: 7956

American (AMR) AF: 0.923 AC: 23249 AN: 25188

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 7163 AN: 8544

East Asian (EAS) AF: 0.883 AC: 7969 AN: 9030

South Asian (SAS) AF: 0.884 AC: 47725 AN: 53974

European-Finnish (FIN) AF: 0.891 AC: 22961 AN: 25764

Middle Eastern (MID) AF: 0.845 AC: 1682 AN: 1990

European-Non Finnish (NFE) AF: 0.858 AC: 122563 AN: 142914

Other (OTH) AF: 0.864 AC: 11233 AN: 12998

GnomAD4 genome AF: 0.896 AC: 136509 AN: 152276 Hom.: 61324 Cov.: 33 AF XY: 0.899 AC XY: 66916 AN XY: 74440

African (AFR) AF: 0.968 AC: 40258 AN: 41568

American (AMR) AF: 0.901 AC: 13782 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2889 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4556 AN: 5178

South Asian (SAS) AF: 0.877 AC: 4229 AN: 4820

European-Finnish (FIN) AF: 0.895 AC: 9495 AN: 10608

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58387 AN: 68006

Other (OTH) AF: 0.871 AC: 1844 AN: 2116

Alfa AF: 0.895 Hom.: 9049

Bravo AF: 0.900

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.24
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9974172; hg19: chr21-46354055;