14-81203689-G-T

Variant names:

• chr14-81203689-G-T
• rs1864169
• NM_015859.4:c.337+211C>A

Variant summary

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

The NM_015859.4(GTF2A1):​c.337+211C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,056 control chromosomes in the GnomAD database, including 46,328 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 0.77 (46328 hom., cov: 31)
• Consequence: GTF2A1 NM_015859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 4 publications found

Genes affected

GTF2A1 (HGNC:4646): (general transcription factor IIA subunit 1) Accurate transcription initiation on TATA-containing class II genes involves the ordered assembly of RNA polymerase II (POLR2A; MIM 180660) and several general initiation factors (summarized by DeJong and Roeder, 1993 [PubMed 8224848]). One of these factors is TFIIA, which when purified from HeLa extracts consists of 35-, 19-, and 12-kD subunits.[supplied by OMIM, Jul 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015859.4. 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
	GTF2A1	NM_015859.4	MANE Select	c.337+211C>A		intron	N/A	NP_056943.1
	GTF2A1	NM_201595.3		c.220+211C>A		intron	N/A	NP_963889.1
	GTF2A1	NM_001278940.2		c.187+211C>A		intron	N/A	NP_001265869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A1	ENST00000553612.6	TSL:1 MANE Select	c.337+211C>A		intron	N/A	ENSP00000452454.1
	GTF2A1	ENST00000434192.2	TSL:1	c.220+211C>A		intron	N/A	ENSP00000409492.2
	GTF2A1	ENST00000298173.7	TSL:2	n.*224+211C>A		intron	N/A	ENSP00000298173.3

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117551 AN: 151938 Hom.: 46305 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.774 AC: 117619 AN: 152056 Hom.: 46328 Cov.: 31 AF XY: 0.763 AC XY: 56692 AN XY: 74288

African (AFR) AF: 0.887 AC: 36829 AN: 41518

American (AMR) AF: 0.658 AC: 10039 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3016 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2200 AN: 5164

South Asian (SAS) AF: 0.643 AC: 3100 AN: 4818

European-Finnish (FIN) AF: 0.722 AC: 7596 AN: 10524

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52264 AN: 67988

Other (OTH) AF: 0.768 AC: 1623 AN: 2114

Alfa AF: 0.777 Hom.: 16047

Bravo AF: 0.777

Asia WGS AF: 0.542 AC: 1884 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.66
DANN	Benign	0.62
PhyloP100		-0.042
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: rs1864169; hg19: chr14-81670033; COSMIC: COSV53338957; COSMIC: COSV53338957;