rs2272300

Variant names:

• chr12-53193684-T-G
• rs2272300
• NM_001004304.4:c.*6094T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004304.4. 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
	ZNF740	NM_001004304.4	MANE Select	c.*6094T>G		3_prime_UTR	Exon 7 of 7	NP_001004304.1	Q8NDX6
	ITGB7	NM_000889.3	MANE Select	c.1502+24A>C		intron	N/A	NP_000880.1	P26010-1
	ITGB7	NM_001414156.1		c.1502+24A>C		intron	N/A	NP_001401085.1	P26010-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF740	ENST00000416904.5	TSL:1 MANE Select	c.*6094T>G		3_prime_UTR	Exon 7 of 7	ENSP00000409463.2	Q8NDX6
	ITGB7	ENST00000267082.10	TSL:1 MANE Select	c.1502+24A>C		intron	N/A	ENSP00000267082.4	P26010-1
	ITGB7	ENST00000422257.7	TSL:5	c.1502+24A>C		intron	N/A	ENSP00000408741.3	P26010-1

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

GnomAD2 exomes AF: 0.141 AC: 32124 AN: 228348 AF XY: 0.137

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 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

African (AFR) AF: 0.495 AC: 16130 AN: 32570

American (AMR) AF: 0.0666 AC: 2741 AN: 41176

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3426 AN: 24198

East Asian (EAS) AF: 0.175 AC: 6888 AN: 39312

South Asian (SAS) AF: 0.208 AC: 17048 AN: 81806

European-Finnish (FIN) AF: 0.131 AC: 6884 AN: 52396

Middle Eastern (MID) AF: 0.118 AC: 614 AN: 5182

European-Non Finnish (NFE) AF: 0.0793 AC: 86618 AN: 1092694

Other (OTH) AF: 0.126 AC: 7426 AN: 58888

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

African (AFR) AF: 0.476 AC: 19685 AN: 41340

American (AMR) AF: 0.103 AC: 1580 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3466

East Asian (EAS) AF: 0.164 AC: 846 AN: 5152

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1406 AN: 10558

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.0867 AC: 5891 AN: 67946

Other (OTH) AF: 0.174 AC: 367 AN: 2104

Alfa AF: 0.116 Hom.: 1640

Bravo AF: 0.214

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272300; hg19: chr12-53587468; COSMIC: COSV57238107; COSMIC: COSV57238107;