rs237238

Variant names:

• chr7-75582098-A-G
• rs237238
• NM_005338.7:c.519T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-75582098-A-G
• chr7-75582098-A-C
• chr7-75582098-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005338.7(HIP1):​c.519T>C​(p.Ala173Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 1,613,564 control chromosomes in the GnomAD database, including 5,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.080 (522 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4496 hom.)
• Consequence: HIP1 NM_005338.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.80
• Publications: 23 publications found

Genes affected

HIP1 (HGNC:4913): (huntingtin interacting protein 1) The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000294540 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-75582098-A-G is Benign according to our data. Variant chr7-75582098-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059356.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005338.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	NM_005338.7	MANE Select	c.519T>C	p.Ala173Ala	synonymous	Exon 6 of 31	NP_005329.3
	HIP1	NM_001382445.1		c.432T>C	p.Ala144Ala	synonymous	Exon 6 of 31	NP_001369374.1	O00291-4
	HIP1	NM_001382444.1		c.417T>C	p.Ala139Ala	synonymous	Exon 6 of 31	NP_001369373.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	ENST00000336926.11	TSL:1 MANE Select	c.519T>C	p.Ala173Ala	synonymous	Exon 6 of 31	ENSP00000336747.6	O00291-1
	HIP1	ENST00000616821.4	TSL:1	c.432T>C	p.Ala144Ala	synonymous	Exon 6 of 31	ENSP00000484528.1	O00291-4
	HIP1	ENST00000857520.1		c.519T>C	p.Ala173Ala	synonymous	Exon 6 of 31	ENSP00000527579.1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12204 AN: 152054 Hom.: 518 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0832

GnomAD2 exomes AF: 0.0796 AC: 19944 AN: 250700 AF XY: 0.0834

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0582

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.0683

Gnomad FIN exome AF: 0.0693

Gnomad NFE exome AF: 0.0708

Gnomad OTH exome AF: 0.0751

GnomAD4 exome AF: 0.0740 AC: 108134 AN: 1461392 Hom.: 4496 Cov.: 31 AF XY: 0.0765 AC XY: 55626 AN XY: 727020

African (AFR) AF: 0.102 AC: 3419 AN: 33466

American (AMR) AF: 0.0603 AC: 2695 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0535 AC: 1399 AN: 26128

East Asian (EAS) AF: 0.0530 AC: 2105 AN: 39694

South Asian (SAS) AF: 0.152 AC: 13129 AN: 86194

European-Finnish (FIN) AF: 0.0704 AC: 3759 AN: 53414

Middle Eastern (MID) AF: 0.116 AC: 668 AN: 5768

European-Non Finnish (NFE) AF: 0.0686 AC: 76302 AN: 1111680

Other (OTH) AF: 0.0772 AC: 4658 AN: 60372

GnomAD4 genome AF: 0.0803 AC: 12223 AN: 152172 Hom.: 522 Cov.: 32 AF XY: 0.0813 AC XY: 6050 AN XY: 74402

African (AFR) AF: 0.100 AC: 4171 AN: 41516

American (AMR) AF: 0.0633 AC: 966 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3470

East Asian (EAS) AF: 0.0726 AC: 375 AN: 5164

South Asian (SAS) AF: 0.156 AC: 752 AN: 4824

European-Finnish (FIN) AF: 0.0708 AC: 751 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4775 AN: 68004

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0735 Hom.: 1504

Bravo AF: 0.0777

Asia WGS AF: 0.109 AC: 377 AN: 3478

EpiCase AF: 0.0714

EpiControl AF: 0.0708

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HIP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-1.8
Mutation Taster		=99/1	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: rs237238; hg19: chr7-75211414;