rs2272300

chr12-53193684-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004304.4(ZNF740):c.*6094T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,580,096 control chromosomes in the GnomAD database, including 17,072 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 (5408 hom., cov: 31)
  • Exomes 𝑓: 0.10 (11664 hom.)
• Consequence: ZNF740 NM_001004304.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF740	NM_001004304.4	c.*6094T>G		3_prime_UTR_variant	7/7	ENST00000416904.5
ITGB7	NM_000889.3	c.1502+24A>C		intron_variant		ENST00000267082.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF740	ENST00000416904.5	c.*6094T>G		3_prime_UTR_variant	7/7	1	NM_001004304.4	P1
ITGB7	ENST00000267082.10	c.1502+24A>C		intron_variant		1	NM_000889.3	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31475 AN: 151756 Hom.: 5386 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.141 AC: 32124 AN: 228348 Hom.: 3504 AF XY: 0.137 AC XY: 16798 AN XY: 122728

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.0612

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.162

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.0921

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.103 AC: 147775 AN: 1428222 Hom.: 11664 Cov.: 31 AF XY: 0.105 AC XY: 74485 AN XY: 706948

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.0666

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0793

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.208 AC: 31553 AN: 151874 Hom.: 5408 Cov.: 31 AF XY: 0.208 AC XY: 15406 AN XY: 74224

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.174

Alfa AF: 0.119 Hom.: 1059

Bravo AF: 0.214

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.2
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272300; hg19: chr12-53587468; COSMIC: COSV57238107; COSMIC: COSV57238107;