14-99667605-T-C

Position:

• chr14-99667605-T-C

Variant summary

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

The NM_001127258.3(HHIPL1):​c.1649-617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,078 control chromosomes in the GnomAD database, including 10,357 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 0.36 (10357 hom., cov: 32)
• Consequence: HHIPL1 NM_001127258.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

Genes affected

HHIPL1 (HGNC:19710): (HHIP like 1) This gene encodes a protein that belongs to the glucose/sorbosone dehydrogenase family. The encoded protein also contains a domain that binds folate and reduced folic acid derivatives. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHIPL1	NM_001127258.3	c.1649-617T>C		intron_variant		ENST00000330710.10	NP_001120730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHIPL1	ENST00000330710.10	c.1649-617T>C		intron_variant		1	NM_001127258.3	ENSP00000330601.5
HHIPL1	ENST00000357223.2	c.1649-617T>C		intron_variant		1		ENSP00000349757.2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54459 AN: 151960 Hom.: 10354 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54475 AN: 152078 Hom.: 10357 Cov.: 32 AF XY: 0.358 AC XY: 26617 AN XY: 74332

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.331

Alfa AF: 0.403 Hom.: 18856

Bravo AF: 0.338

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2895811; hg19: chr14-100133942;