2-200821399-T-C

Variant names:

• chr2-200821399-T-C
• rs3815501
• NM_001207067.2:c.1228+94T>C

Variant summary

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

The NM_001207067.2(BZW1):​c.1228+94T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,473,268 control chromosomes in the GnomAD database, including 471,296 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 0.78 (46618 hom., cov: 32)
  • Exomes 𝑓: 0.80 (424678 hom.)
• Consequence: BZW1 NM_001207067.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 12 publications found

Genes affected

BZW1 (HGNC:18380): (basic leucine zipper and W2 domains 1) Enables RNA binding activity and cadherin binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207067.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW1	NM_001207067.2	MANE Select	c.1228+94T>C		intron	N/A	NP_001193996.1
	BZW1	NM_001207068.3		c.1324+94T>C		intron	N/A	NP_001193997.1
	BZW1	NM_001207069.2		c.1240+94T>C		intron	N/A	NP_001193998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BZW1	ENST00000409600.6	TSL:1 MANE Select	c.1228+94T>C		intron	N/A	ENSP00000386474.1
	BZW1	ENST00000452790.6	TSL:2	c.1324+94T>C		intron	N/A	ENSP00000394316.2
	BZW1	ENST00000409226.5	TSL:2	c.1240+94T>C		intron	N/A	ENSP00000386837.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118309 AN: 152022 Hom.: 46593 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.796 AC: 1052269 AN: 1321128 Hom.: 424678 AF XY: 0.792 AC XY: 518826 AN XY: 655294

African (AFR) AF: 0.773 AC: 23070 AN: 29830

American (AMR) AF: 0.596 AC: 20569 AN: 34528

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 17614 AN: 22154

East Asian (EAS) AF: 0.446 AC: 16985 AN: 38088

South Asian (SAS) AF: 0.612 AC: 44131 AN: 72150

European-Finnish (FIN) AF: 0.800 AC: 30882 AN: 38624

Middle Eastern (MID) AF: 0.765 AC: 3939 AN: 5148

European-Non Finnish (NFE) AF: 0.831 AC: 852197 AN: 1025464

Other (OTH) AF: 0.778 AC: 42882 AN: 55142

GnomAD4 genome AF: 0.778 AC: 118379 AN: 152140 Hom.: 46618 Cov.: 32 AF XY: 0.768 AC XY: 57143 AN XY: 74376

African (AFR) AF: 0.780 AC: 32371 AN: 41492

American (AMR) AF: 0.685 AC: 10482 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2765 AN: 3466

East Asian (EAS) AF: 0.482 AC: 2493 AN: 5176

South Asian (SAS) AF: 0.589 AC: 2836 AN: 4812

European-Finnish (FIN) AF: 0.792 AC: 8369 AN: 10570

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.830 AC: 56466 AN: 68016

Other (OTH) AF: 0.778 AC: 1639 AN: 2106

Alfa AF: 0.806 Hom.: 104021

Bravo AF: 0.773

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3815501; hg19: chr2-201686122; COSMIC: COSV63350596; COSMIC: COSV63350596;