rs1859168

Variant names:

• chr7-27202740-A-C
• rs1859168
• ENST00000472494.2:n.2214A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-27202740-A-C
• chr7-27202740-A-G
• chr7-27202740-A-T

Variant summary

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

The ENST00000472494.2(HOTTIP):​n.2214A>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 0.923 in 148,694 control chromosomes in the GnomAD database, including 63,706 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 0.92 (63699 hom., cov: 22)
  • Exomes 𝑓: 0.94 (7 hom.)
• Consequence: HOTTIP ENST00000472494.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 40 publications found

Genes affected

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

ENSG00000277469 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOTTIP	NR_037843.3	n.2117+102A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOTTIP	ENST00000472494.2	n.2214A>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
HOTTIP	ENST00000521028.4	n.795+102A>C		intron_variant	Intron 1 of 1	5
HOTTIP	ENST00000814986.1	n.206+102A>C		intron_variant	Intron 1 of 1
ENSG00000277469	ENST00000619957.1	n.*102A>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.923 AC: 137132 AN: 148568 Hom.: 63654 Cov.: 22

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.926

GnomAD4 exome AF: 0.938 AC: 15 AN: 16 Hom.: 7 Cov.: 0 AF XY: 0.917 AC XY: 11 AN XY: 12

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.938 AC: 15 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.923 AC: 137232 AN: 148678 Hom.: 63699 Cov.: 22 AF XY: 0.919 AC XY: 66472 AN XY: 72340

African (AFR) AF: 0.982 AC: 39672 AN: 40414

American (AMR) AF: 0.873 AC: 12939 AN: 14824

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3324 AN: 3458

East Asian (EAS) AF: 0.598 AC: 3005 AN: 5026

South Asian (SAS) AF: 0.916 AC: 4145 AN: 4526

European-Finnish (FIN) AF: 0.902 AC: 8939 AN: 9912

Middle Eastern (MID) AF: 0.979 AC: 282 AN: 288

European-Non Finnish (NFE) AF: 0.926 AC: 62283 AN: 67288

Other (OTH) AF: 0.925 AC: 1897 AN: 2050

Alfa AF: 0.911 Hom.: 19614

Bravo AF: 0.922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.4
DANN	Benign	0.67
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs1859168; hg19: chr7-27242359;