rs1537632

Variant names:

• chr10-7575847-T-C
• rs1537632
• NM_030569.7:c.1978+606A>G

Variant summary

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

The NM_030569.7(ITIH5):​c.1978+606A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,120 control chromosomes in the GnomAD database, including 3,651 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 0.21 (3651 hom., cov: 33)
• Consequence: ITIH5 NM_030569.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 3 publications found

Genes affected

ITIH5 (HGNC:21449): (inter-alpha-trypsin inhibitor heavy chain 5) This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

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 = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITIH5	NM_030569.7	c.1978+606A>G		intron_variant	Intron 10 of 13	ENST00000397146.7	NP_085046.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH5	ENST00000397146.7	c.1978+606A>G		intron_variant	Intron 10 of 13	1	NM_030569.7	ENSP00000380333.3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32229 AN: 152002 Hom.: 3647 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.212 AC: 32244 AN: 152120 Hom.: 3651 Cov.: 33 AF XY: 0.213 AC XY: 15806 AN XY: 74360

African (AFR) AF: 0.279 AC: 11590 AN: 41478

American (AMR) AF: 0.138 AC: 2109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.164 AC: 851 AN: 5184

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4808

European-Finnish (FIN) AF: 0.219 AC: 2310 AN: 10572

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13069 AN: 67994

Other (OTH) AF: 0.197 AC: 416 AN: 2114

Alfa AF: 0.194 Hom.: 12554

Bravo AF: 0.209

Asia WGS AF: 0.231 AC: 801 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	1.3
DANN	Benign	0.76
PhyloP100		0.24
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: rs1537632; hg19: chr10-7617810;