rs1537626

Variant names:

• chr10-7611161-G-A
• rs1537626
• NM_030569.7:c.939+4821C>T

Variant summary

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

The NM_030569.7(ITIH5):​c.939+4821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,212 control chromosomes in the GnomAD database, including 3,723 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 0.22 (3723 hom., cov: 33)
• Consequence: ITIH5 NM_030569.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030569.7. 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
	ITIH5	NM_030569.7	MANE Select	c.939+4821C>T		intron	N/A	NP_085046.5
	ITIH5	NM_032817.6		c.297+4821C>T		intron	N/A	NP_116206.4
	ITIH5	NM_001001851.3		c.939+4821C>T		intron	N/A	NP_001001851.1	G5E9D8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH5	ENST00000397146.7	TSL:1 MANE Select	c.939+4821C>T		intron	N/A	ENSP00000380333.3	C9J2H1
	ITIH5	ENST00000613909.4	TSL:1	c.297+4821C>T		intron	N/A	ENSP00000485414.1	A0A096LP62
	ITIH5	ENST00000884049.1		c.940-1667C>T		intron	N/A	ENSP00000554108.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33065 AN: 152094 Hom.: 3714 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.218 AC: 33120 AN: 152212 Hom.: 3723 Cov.: 33 AF XY: 0.218 AC XY: 16252 AN XY: 74418

African (AFR) AF: 0.198 AC: 8242 AN: 41532

American (AMR) AF: 0.168 AC: 2574 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1075 AN: 5186

South Asian (SAS) AF: 0.161 AC: 779 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3202 AN: 10582

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15670 AN: 68010

Other (OTH) AF: 0.223 AC: 472 AN: 2114

Alfa AF: 0.221 Hom.: 4817

Bravo AF: 0.206

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1537626; hg19: chr10-7653124;