rs1202437

Variant names:

• chr7-149145466-C-T
• rs1202437
• ENST00000426851.6:c.-489-8479C>T

Variant summary

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

The ENST00000426851.6(ZNF398):​c.-489-8479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,092 control chromosomes in the GnomAD database, including 2,480 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 0.17 (2480 hom., cov: 32)
• Consequence: ZNF398 ENST00000426851.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 11 publications found

Genes affected

ZNF398 (HGNC:18373): (zinc finger protein 398) This gene encodes a member of the Kruppel family of C2H2-type zinc-finger transcription factor proteins. The encoded protein acts as a transcriptional activator. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described, but their full length sequence has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000306533 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986856	XR_001745398.3	n.1146G>A		non_coding_transcript_exon_variant	Exon 2 of 2
LOC107986856	XR_007060581.1	n.1266G>A		non_coding_transcript_exon_variant	Exon 2 of 2
ZNF398	NM_020781.4	c.-489-8479C>T		intron_variant	Intron 2 of 6		NP_065832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF398	ENST00000426851.6	c.-489-8479C>T		intron_variant	Intron 2 of 6	1		ENSP00000389972.2
ENSG00000306533	ENST00000819240.1	n.1147G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25850 AN: 151974 Hom.: 2474 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.170 AC: 25880 AN: 152092 Hom.: 2480 Cov.: 32 AF XY: 0.164 AC XY: 12185 AN XY: 74350

African (AFR) AF: 0.241 AC: 10009 AN: 41470

American (AMR) AF: 0.134 AC: 2040 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0573 AC: 276 AN: 4814

European-Finnish (FIN) AF: 0.113 AC: 1193 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11211 AN: 67988

Other (OTH) AF: 0.166 AC: 350 AN: 2112

Alfa AF: 0.171 Hom.: 4114

Bravo AF: 0.175

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1202437; hg19: chr7-148842558; COSMIC: COSV69652947; COSMIC: COSV69652947;