rs782523521

Variant names:

• chr7-75149075-G-C
• rs782523521
• NM_001003795.3:c.2628G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-75149075-G-C
• chr7-75149075-G-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.2628G>C​(p.Thr876Thr) 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 0.000082 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2IRD2B NM_001003795.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300
• 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=-0.5).
• BP6: Variant 7-75149075-G-C is Benign according to our data. Variant chr7-75149075-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2657608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.03 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.2628G>C	p.Thr876Thr	synonymous	Exon 16 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.3114G>C	p.Thr1038Thr	synonymous	Exon 16 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.2628G>C	p.Thr876Thr	synonymous	Exon 16 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000418185.6	TSL:1	n.*1903G>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000411454.3	Q6EKJ0-2
	GTF2IRD2B	ENST00000611835.4	TSL:1	n.2316G>C		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.0000819 AC: 12 AN: 146522 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000750

Gnomad OTH AF: 0.000508

GnomAD2 exomes AF: 0.000114 AC: 7 AN: 61432 AF XY: 0.000162

Gnomad AFR exome AF: 0.00

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: 0.000233 AC: 164 AN: 703846 Hom.: 0 Cov.: 9 AF XY: 0.000309 AC XY: 117 AN XY: 378116

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

African (AFR) AF: 0.00 AC: 0 AN: 19248

American (AMR) AF: 0.00 AC: 0 AN: 43814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21486

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36380

South Asian (SAS) AF: 0.00138 AC: 98 AN: 71198

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2692

European-Non Finnish (NFE) AF: 0.000140 AC: 59 AN: 420506

Other (OTH) AF: 0.000141 AC: 5 AN: 35364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000818 AC: 12 AN: 146632 Hom.: 0 Cov.: 23 AF XY: 0.000113 AC XY: 8 AN XY: 71058

African (AFR) AF: 0.0000253 AC: 1 AN: 39566

American (AMR) AF: 0.00 AC: 0 AN: 14420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4890

South Asian (SAS) AF: 0.00113 AC: 5 AN: 4436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000750 AC: 5 AN: 66686

Other (OTH) AF: 0.000502 AC: 1 AN: 1992

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	-0.50
CADD	Benign	4.4
DANN	Benign	0.60
PhyloP100		-0.030

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: rs782523521; hg19: chr7-74564881;