19-6552375-C-T

Variant names:

• chr19-6552375-C-T
• rs348384
• ENST00000594355.1:n.523G>A

Variant summary

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

The ENST00000594355.1(TGFBR1P1):​n.523G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,864 control chromosomes in the GnomAD database, including 4,269 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 0.22 (4267 hom., cov: 32)
  • Exomes 𝑓: 0.087 (2 hom.)
• Consequence: TGFBR1P1 ENST00000594355.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• Publications: 4 publications found

Genes affected

TGFBR1P1 (HGNC:56999):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR1P1	ENST00000594355.1	n.523G>A		non_coding_transcript_exon_variant	Exon 3 of 3	6

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33064 AN: 152060 Hom.: 4263 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.0875 AC: 60 AN: 686 Hom.: 2 Cov.: 0 AF XY: 0.0909 AC XY: 40 AN XY: 440

⚠️ 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: 6

American (AMR) AF: 0.208 AC: 5 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0429 AC: 3 AN: 70

European-Finnish (FIN) AF: 0.0577 AC: 3 AN: 52

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0966 AC: 46 AN: 476

Other (OTH) AF: 0.0882 AC: 3 AN: 34

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.217 AC: 33068 AN: 152178 Hom.: 4267 Cov.: 32 AF XY: 0.211 AC XY: 15674 AN XY: 74394

African (AFR) AF: 0.103 AC: 4298 AN: 41530

American (AMR) AF: 0.268 AC: 4097 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3464

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5188

South Asian (SAS) AF: 0.162 AC: 780 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2110 AN: 10598

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20028 AN: 67984

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.252 Hom.: 10814

Bravo AF: 0.218

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs348384; hg19: chr19-6552386;