10-7575847-T-C

Position:

• chr10-7575847-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ITIH5	NM_030569.7	c.1978+606A>G		intron_variant		ENST00000397146.7	NP_085046.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH5	ENST00000397146.7	c.1978+606A>G		intron_variant		1	NM_030569.7	ENSP00000380333	P1

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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.197

Alfa AF: 0.191 Hom.: 5652

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1537632; hg19: chr10-7617810;