chr8-132091043-T-C

Variant names:

• chr8-132091043-T-C
• rs2014357
• NM_001145095.3:c.449-1444A>G

Variant summary

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

The NM_001145095.3(HHLA1):​c.449-1444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,234 control chromosomes in the GnomAD database, including 745 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 0.089 (745 hom., cov: 32)
• Consequence: HHLA1 NM_001145095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHLA1	NM_001145095.3	c.449-1444A>G		intron_variant	Intron 7 of 16	ENST00000414222.2	NP_001138567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHLA1	ENST00000414222.2	c.449-1444A>G		intron_variant	Intron 7 of 16	5	NM_001145095.3	ENSP00000388322.1
HHLA1	ENST00000673615.1	c.557-1444A>G		intron_variant	Intron 8 of 17			ENSP00000500443.1

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13460 AN: 152116 Hom.: 740 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0886 AC: 13484 AN: 152234 Hom.: 745 Cov.: 32 AF XY: 0.0930 AC XY: 6924 AN XY: 74432

African (AFR) AF: 0.100 AC: 4155 AN: 41556

American (AMR) AF: 0.0866 AC: 1325 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4828

European-Finnish (FIN) AF: 0.0913 AC: 968 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0645 AC: 4383 AN: 68006

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0752 Hom.: 1943

Bravo AF: 0.0817

Asia WGS AF: 0.247 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.80
PhyloP100		0.31
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: rs2014357; hg19: chr8-133103290;