7-27200863-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_037843.3(HOTTIP):n.342C>G 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 0.351 in 152,586 control chromosomes in the GnomAD database, including 10,959 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 (10907 hom., cov: 32)
  • Exomes 𝑓: 0.41 (52 hom.)
• Consequence: HOTTIP NR_037843.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOTTIP	NR_037843.3	n.342C>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOTTIP	ENST00000421733.1	n.408C>G		non_coding_transcript_exon_variant	2/2	5
HOTTIP	ENST00000472494.1	n.326C>G		non_coding_transcript_exon_variant	2/2	2
HOTTIP	ENST00000605136.6	n.327C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53315 AN: 151970 Hom.: 10904 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.412 AC: 206 AN: 500 Hom.: 52 Cov.: 0 AF XY: 0.410 AC XY: 110 AN XY: 268

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.351 AC: 53323 AN: 152086 Hom.: 10907 Cov.: 32 AF XY: 0.349 AC XY: 25944 AN XY: 74336

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.402

Alfa AF: 0.392 Hom.: 1589

Bravo AF: 0.336

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.1
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3807598; hg19: chr7-27240482;