rs2721

Variant names:

• chr7-155296033-T-G
• rs2721
• ENST00000609974.2:n.1509A>C

Variant summary

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

The ENST00000609974.2(INSIG1-DT):​n.1509A>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 0.85 in 152,278 control chromosomes in the GnomAD database, including 55,233 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 0.85 (55231 hom., cov: 33)
  • Exomes 𝑓: 0.75 (2 hom.)
• Consequence: INSIG1-DT ENST00000609974.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 10 publications found

Genes affected

INSIG1-DT (HGNC:55155): (INSIG1 divergent transcript)

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 = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSIG1-DT	NR_183446.1	n.1355+271A>C		intron_variant	Intron 1 of 1
INSIG1-DT	NR_183447.1	n.830+2118A>C		intron_variant	Intron 1 of 1
INSIG1-DT	NR_183448.1	n.830+2118A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSIG1-DT	ENST00000609974.2	n.1509A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
INSIG1-DT	ENST00000743985.1	n.1130+271A>C		intron_variant	Intron 1 of 1
INSIG1-DT	ENST00000743986.1	n.707+691A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129311 AN: 152152 Hom.: 55182 Cov.: 33

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.750 AC: 6 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.750 AC XY: 6 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.850 AC: 129420 AN: 152270 Hom.: 55231 Cov.: 33 AF XY: 0.846 AC XY: 62984 AN XY: 74474

African (AFR) AF: 0.902 AC: 37494 AN: 41550

American (AMR) AF: 0.820 AC: 12538 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2742 AN: 3466

East Asian (EAS) AF: 0.727 AC: 3768 AN: 5180

South Asian (SAS) AF: 0.673 AC: 3246 AN: 4824

European-Finnish (FIN) AF: 0.860 AC: 9134 AN: 10626

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57683 AN: 68006

Other (OTH) AF: 0.839 AC: 1774 AN: 2114

Alfa AF: 0.862 Hom.: 8038

Bravo AF: 0.852

Asia WGS AF: 0.727 AC: 2526 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	0.87
DANN	Benign	0.47
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs2721; hg19: chr7-155087743;