rs11170466

Variant names:

• chr12-53192075-C-T
• rs11170466
• NM_001004304.4:c.*4485C>T

Variant summary

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

The NM_001004304.4(ZNF740):​c.*4485C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,566,724 control chromosomes in the GnomAD database, including 3,223 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 0.059 (354 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2869 hom.)
• Consequence: ZNF740 NM_001004304.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 20 publications found

Genes affected

ZNF740 (HGNC:27465): (zinc finger protein 740) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ITGB7 (HGNC:6162): (integrin subunit beta 7) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms dimers with an alpha4 chain or an alphaE chain and plays a role in leukocyte adhesion. Dimerization with alpha4 forms a homing receptor for migration of lymphocytes to the intestinal mucosa and Peyer's patches. Dimerization with alphaE permits binding to the ligand epithelial cadherin, a calcium-dependent adhesion molecule. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF740	NM_001004304.4	c.*4485C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000416904.5	NP_001004304.1
ITGB7	NM_000889.3	c.2156-56G>A		intron_variant	Intron 14 of 15	ENST00000267082.10	NP_000880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF740	ENST00000416904.5	c.*4485C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001004304.4	ENSP00000409463.2
ITGB7	ENST00000267082.10	c.2156-56G>A		intron_variant	Intron 14 of 15	1	NM_000889.3	ENSP00000267082.4

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9026 AN: 152082 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0578 AC: 81704 AN: 1414524 Hom.: 2869 Cov.: 27 AF XY: 0.0573 AC XY: 40197 AN XY: 701280

African (AFR) AF: 0.0367 AC: 1187 AN: 32322

American (AMR) AF: 0.0271 AC: 1087 AN: 40132

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2655 AN: 24404

East Asian (EAS) AF: 0.174 AC: 6774 AN: 38932

South Asian (SAS) AF: 0.0313 AC: 2600 AN: 82974

European-Finnish (FIN) AF: 0.115 AC: 5654 AN: 49202

Middle Eastern (MID) AF: 0.0633 AC: 312 AN: 4928

European-Non Finnish (NFE) AF: 0.0534 AC: 57825 AN: 1083366

Other (OTH) AF: 0.0620 AC: 3610 AN: 58264

GnomAD4 genome AF: 0.0593 AC: 9023 AN: 152200 Hom.: 354 Cov.: 32 AF XY: 0.0617 AC XY: 4592 AN XY: 74410

African (AFR) AF: 0.0350 AC: 1456 AN: 41542

American (AMR) AF: 0.0338 AC: 516 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.160 AC: 825 AN: 5156

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1268 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0606 AC: 4118 AN: 68006

Other (OTH) AF: 0.0553 AC: 117 AN: 2116

Alfa AF: 0.0602 Hom.: 510

Bravo AF: 0.0517

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.56
PhyloP100		0.14
PromoterAI		-0.056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs11170466; hg19: chr12-53585859;