7-75112506-C-A

Variant names:

• chr7-75112506-C-A
• rs1440249591
• NM_001003795.3:c.209C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003795.3(GTF2IRD2B):​c.209C>A​(p.Thr70Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T70M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 7)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022388577).

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.209C>A	p.Thr70Lys	missense	Exon 3 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.695C>A	p.Thr232Lys	missense	Exon 3 of 16	NP_001355231.1
	GTF2IRD2B	NM_001368301.1		c.209C>A	p.Thr70Lys	missense	Exon 3 of 3	NP_001355230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD2B	ENST00000472837.7	TSL:1 MANE Select	c.209C>A	p.Thr70Lys	missense	Exon 3 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000619142.4	TSL:1	c.209C>A	p.Thr70Lys	missense	Exon 3 of 16	ENSP00000480037.1	A0A087WW90
	GTF2IRD2B	ENST00000614064.4	TSL:1	c.209C>A	p.Thr70Lys	missense	Exon 3 of 3	ENSP00000481706.1

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 852324 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 444150

⚠️ 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: 19638

American (AMR) AF: 0.00 AC: 0 AN: 37564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20696

East Asian (EAS) AF: 0.00 AC: 0 AN: 34282

South Asian (SAS) AF: 0.00 AC: 0 AN: 71402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2844

European-Non Finnish (NFE) AF: 0.00000174 AC: 1 AN: 575484

Other (OTH) AF: 0.00 AC: 0 AN: 39626

⚠️ 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 Cov.: 7

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.9
DANN	Benign	0.20
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.043
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.32		Loss of ubiquitination at K74 (P = 0.0331)
MVP		0.014
ClinPred		0.021	T
GERP RS		-5.6
Varity_R		0.052
gMVP		0.048
Mutation Taster		=95/5	polymorphism

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: rs1440249591; hg19: chr7-74528300;