14-99667605-T-C

Variant names:

• chr14-99667605-T-C
• rs2895811
• NM_001127258.3:c.1649-617T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 107 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127258.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIPL1	NM_001127258.3	MANE Select	c.1649-617T>C		intron	N/A	NP_001120730.1
	HHIPL1	NM_032425.5		c.1649-617T>C		intron	N/A	NP_115801.3
	HHIPL1	NM_001329411.2		c.1454-617T>C		intron	N/A	NP_001316340.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIPL1	ENST00000330710.10	TSL:1 MANE Select	c.1649-617T>C		intron	N/A	ENSP00000330601.5
	HHIPL1	ENST00000357223.2	TSL:1	c.1649-617T>C		intron	N/A	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

African (AFR) AF: 0.246 AC: 10204 AN: 41506

American (AMR) AF: 0.321 AC: 4900 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1309 AN: 5160

South Asian (SAS) AF: 0.452 AC: 2173 AN: 4810

European-Finnish (FIN) AF: 0.440 AC: 4653 AN: 10586

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28886 AN: 67958

Other (OTH) AF: 0.331 AC: 696 AN: 2100

Alfa AF: 0.399 Hom.: 39616

Bravo AF: 0.338

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.85
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2895811; hg19: chr14-100133942;