8-132102752-C-T

Variant names:

• chr8-132102752-C-T
• rs715257
• NM_001145095.3:c.139+1356G>A

Variant summary

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

The NM_001145095.3(HHLA1):​c.139+1356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,250 control chromosomes in the GnomAD database, including 27,682 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 0.60 (27682 hom., cov: 29)
• Consequence: HHLA1 NM_001145095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 publications found

Genes affected

HHLA1 (HGNC:4904): (HHLA1 neighbor of OC90) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHLA1	NM_001145095.3	c.139+1356G>A		intron_variant	Intron 3 of 16	ENST00000414222.2	NP_001138567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHLA1	ENST00000414222.2	c.139+1356G>A		intron_variant	Intron 3 of 16	5	NM_001145095.3	ENSP00000388322.1
HHLA1	ENST00000673615.1	c.174+1321G>A		intron_variant	Intron 3 of 17			ENSP00000500443.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91233 AN: 151140 Hom.: 27660 Cov.: 29

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.604 AC: 91302 AN: 151250 Hom.: 27682 Cov.: 29 AF XY: 0.603 AC XY: 44513 AN XY: 73786

African (AFR) AF: 0.644 AC: 26554 AN: 41202

American (AMR) AF: 0.639 AC: 9732 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2363 AN: 5094

South Asian (SAS) AF: 0.487 AC: 2324 AN: 4774

European-Finnish (FIN) AF: 0.629 AC: 6495 AN: 10328

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.592 AC: 40157 AN: 67866

Other (OTH) AF: 0.569 AC: 1191 AN: 2094

Alfa AF: 0.550 Hom.: 3572

Bravo AF: 0.608

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.76
PhyloP100		-1.0
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: rs715257; hg19: chr8-133114999;