chr7-75123250-A-C

Variant names:

• chr7-75123250-A-C
• rs782200678
• NM_001003795.3:c.473A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001003795.3(GTF2IRD2B):​c.473A>C​(p.Glu158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E158D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00016 (5 hom.)
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03570631).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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.473A>C	p.Glu158Ala	missense	Exon 5 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.959A>C	p.Glu320Ala	missense	Exon 5 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.473A>C	p.Glu158Ala	missense	Exon 5 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000619142.4	TSL:1	c.473A>C	p.Glu158Ala	missense	Exon 5 of 16	ENSP00000480037.1	A0A087WW90
	GTF2IRD2B	ENST00000418185.6	TSL:1	n.473A>C		non_coding_transcript_exon	Exon 5 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes AF: 0.000175 AC: 22 AN: 126008 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000328

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: 0.000132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000326

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000150 AC: 29 AN: 193376 AF XY: 0.000187

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: 0.000428

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.000220

GnomAD4 exome AF: 0.000160 AC: 204 AN: 1278570 Hom.: 5 Cov.: 20 AF XY: 0.000162 AC XY: 103 AN XY: 637668

African (AFR) AF: 0.00 AC: 0 AN: 26384

American (AMR) AF: 0.00 AC: 0 AN: 31528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22914

East Asian (EAS) AF: 0.00 AC: 0 AN: 38618

South Asian (SAS) AF: 0.00 AC: 0 AN: 75720

European-Finnish (FIN) AF: 0.000474 AC: 24 AN: 50638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3652

European-Non Finnish (NFE) AF: 0.000175 AC: 171 AN: 975570

Other (OTH) AF: 0.000168 AC: 9 AN: 53546

GnomAD4 genome AF: 0.000175 AC: 22 AN: 126008 Hom.: 0 Cov.: 18 AF XY: 0.000150 AC XY: 9 AN XY: 59874

African (AFR) AF: 0.0000328 AC: 1 AN: 30480

American (AMR) AF: 0.00 AC: 0 AN: 12234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3216

East Asian (EAS) AF: 0.00 AC: 0 AN: 4656

South Asian (SAS) AF: 0.00 AC: 0 AN: 3788

European-Finnish (FIN) AF: 0.000132 AC: 1 AN: 7556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.000326 AC: 20 AN: 61318

Other (OTH) AF: 0.00 AC: 0 AN: 1636

Alfa AF: 0.000245 Hom.: 0

ExAC AF: 0.000118 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.098
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.19	T
Polyphen		0.025	B
Vest4		0.17
MutPred		0.45		Loss of solvent accessibility (P = 0.0769)
MVP		0.014
ClinPred		0.011	T
GERP RS		1.6
Varity_R		0.066
gMVP		0.15
Mutation Taster		=94/6	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: rs782200678; hg19: chr7-74539051;