rs2721965

Variant names:

• chr8-115649811-A-C
• rs2721965
• NM_014112.5:c.-122+18734T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-115649811-A-C
• chr8-115649811-A-T

Variant summary

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

The NM_014112.5(TRPS1):​c.-122+18734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,100 control chromosomes in the GnomAD database, including 7,555 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 0.30 (7555 hom., cov: 33)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 14 publications found

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

TRPS1 Gene-Disease associations (from GenCC):

• trichorhinophalangeal syndrome type I

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• trichorhinophalangeal syndrome, type III

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• trichorhinophalangeal syndrome type I or III

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+18734T>G		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+18734T>G		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.10+18063T>G		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-3+18734T>G		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+18734T>G		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45482 AN: 151980 Hom.: 7544 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.299 AC: 45509 AN: 152100 Hom.: 7555 Cov.: 33 AF XY: 0.308 AC XY: 22880 AN XY: 74342

African (AFR) AF: 0.174 AC: 7219 AN: 41520

American (AMR) AF: 0.391 AC: 5973 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5158

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4820

European-Finnish (FIN) AF: 0.460 AC: 4856 AN: 10560

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22130 AN: 67976

Other (OTH) AF: 0.273 AC: 577 AN: 2114

Alfa AF: 0.305 Hom.: 9604

Bravo AF: 0.292

Asia WGS AF: 0.341 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		0.85
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: rs2721965; hg19: chr8-116662038;