5-51383180-A-G

Variant names:

• chr5-51383180-A-G
• rs3762977
• ENST00000559112.3:n.153T>C

Variant summary

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

The ENST00000559112.3(ISL1-DT):​n.153T>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 0.141 in 169,626 control chromosomes in the GnomAD database, including 1,997 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 0.15 (1872 hom., cov: 32)
  • Exomes 𝑓: 0.091 (125 hom.)
• Consequence: ISL1-DT ENST00000559112.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 11 publications found

Genes affected

ISL1-DT (HGNC:55414): (ISL1 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISL1-DT	NR_046243.1	n.153T>C		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISL1-DT	ENST00000559112.3	n.153T>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
ISL1-DT	ENST00000820577.1	n.84T>C		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22262 AN: 151836 Hom.: 1866 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0261

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.0908 AC: 1605 AN: 17674 Hom.: 125 Cov.: 0 AF XY: 0.0922 AC XY: 862 AN XY: 9346

African (AFR) AF: 0.180 AC: 27 AN: 150

American (AMR) AF: 0.0701 AC: 154 AN: 2196

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 23 AN: 206

East Asian (EAS) AF: 0.00974 AC: 9 AN: 924

South Asian (SAS) AF: 0.120 AC: 198 AN: 1644

European-Finnish (FIN) AF: 0.0705 AC: 32 AN: 454

Middle Eastern (MID) AF: 0.109 AC: 7 AN: 64

European-Non Finnish (NFE) AF: 0.0961 AC: 1076 AN: 11200

Other (OTH) AF: 0.0945 AC: 79 AN: 836

GnomAD4 genome AF: 0.147 AC: 22273 AN: 151952 Hom.: 1872 Cov.: 32 AF XY: 0.147 AC XY: 10890 AN XY: 74286

African (AFR) AF: 0.214 AC: 8856 AN: 41466

American (AMR) AF: 0.0938 AC: 1434 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3464

East Asian (EAS) AF: 0.0260 AC: 132 AN: 5074

South Asian (SAS) AF: 0.151 AC: 726 AN: 4816

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10576

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8532 AN: 67958

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.134 Hom.: 173

Bravo AF: 0.144

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.9
PromoterAI		-0.0068	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3762977; hg19: chr5-50679014;