NM_001003795.3:c.816G>A

Variant names:

• chr7-75136795-G-A
• rs1358019701
• NM_001003795.3:c.816G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001003795.3(GTF2IRD2B):​c.816G>A​(p.Pro272Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 13)
  • Exomes 𝑓: 0.0000074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2IRD2B NM_001003795.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.905
• Publications: 0 publications found

Genes affected

GTF2IRD2B (HGNC:33125): (GTF2I repeat domain containing 2B) This gene encodes a glycosylated phosphoprotein with a leucine zipper motif, two helix-loop-helix motifs (I repeats) that are similar to domains found in the TFII-I family of transcription factors, one CHARLIE8 transposable element-like sequence, and a BED zinc finger. This gene lies within a region that is deleted in Williams-Beuren syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-75136795-G-A is Benign according to our data. Variant chr7-75136795-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3778334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.905 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003795.3. 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
	GTF2IRD2B	NM_001003795.3	MANE Select	c.816G>A	p.Pro272Pro	synonymous	Exon 11 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.1302G>A	p.Pro434Pro	synonymous	Exon 11 of 16	NP_001355231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD2B	ENST00000472837.7	TSL:1 MANE Select	c.816G>A	p.Pro272Pro	synonymous	Exon 11 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000619142.4	TSL:1	c.816G>A	p.Pro272Pro	synonymous	Exon 11 of 16	ENSP00000480037.1	A0A087WW90
	GTF2IRD2B	ENST00000418185.6	TSL:1	n.*91G>A		non_coding_transcript_exon	Exon 10 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 2 AN: 101030 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.0000472

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000778

GnomAD2 exomes AF: 0.0000298 AC: 1 AN: 33528 AF XY: 0.00

Gnomad AFR exome AF: 0.000377

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000740 AC: 3 AN: 405440 Hom.: 0 Cov.: 0 AF XY: 0.00000931 AC XY: 2 AN XY: 214724

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000977 AC: 1 AN: 10240

American (AMR) AF: 0.00 AC: 0 AN: 17412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12082

East Asian (EAS) AF: 0.00 AC: 0 AN: 29182

South Asian (SAS) AF: 0.0000230 AC: 1 AN: 43480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1582

European-Non Finnish (NFE) AF: 0.00000419 AC: 1 AN: 238442

Other (OTH) AF: 0.00 AC: 0 AN: 22844

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000359607), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000198 AC: 2 AN: 101092 Hom.: 0 Cov.: 13 AF XY: 0.0000215 AC XY: 1 AN XY: 46528

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000470 AC: 1 AN: 21262

American (AMR) AF: 0.00 AC: 0 AN: 9328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2798

East Asian (EAS) AF: 0.00 AC: 0 AN: 4560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51756

Other (OTH) AF: 0.000770 AC: 1 AN: 1298

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1358019701; hg19: chr7-74552602;