rs10085013

Variant names:

• chr5-136134352-T-A
• rs10085013
• ENST00000297163.4:n.539A>T

Variant summary

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

The ENST00000297163.4(SMAD5-AS1):​n.539A>T 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 0.36 in 152,056 control chromosomes in the GnomAD database, including 10,847 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 0.36 (10845 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: SMAD5-AS1 ENST00000297163.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 9 publications found

Genes affected

SMAD5-AS1 (HGNC:30586): (SMAD5 antisense RNA 1) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

SMAD5 (HGNC:6771): (SMAD family member 5) The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ENSG00000274934 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.-245+1390T>A		intron_variant	Intron 1 of 7	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+1390T>A		intron_variant	Intron 1 of 7	1	NM_005903.7	ENSP00000441954.2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54683 AN: 151874 Hom.: 10816 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.297 AC: 19 AN: 64 Hom.: 2 Cov.: 0 AF XY: 0.295 AC XY: 13 AN XY: 44

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.310 AC: 18 AN: 58

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.360 AC: 54758 AN: 151992 Hom.: 10845 Cov.: 32 AF XY: 0.356 AC XY: 26450 AN XY: 74310

African (AFR) AF: 0.538 AC: 22304 AN: 41442

American (AMR) AF: 0.284 AC: 4338 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1952 AN: 5172

South Asian (SAS) AF: 0.187 AC: 899 AN: 4808

European-Finnish (FIN) AF: 0.302 AC: 3183 AN: 10552

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19805 AN: 67960

Other (OTH) AF: 0.384 AC: 811 AN: 2112

Alfa AF: 0.318 Hom.: 1058

Bravo AF: 0.374

Asia WGS AF: 0.343 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.2
DANN	Benign	0.84
PhyloP100		-1.2
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: rs10085013; hg19: chr5-135470041;