rs7356756

chr5-136135345-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005903.7(SMAD5):c.-245+2383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,098 control chromosomes in the GnomAD database, including 10,860 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 (10860 hom., cov: 32)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD5	NM_005903.7	c.-245+2383T>C		intron_variant		ENST00000545279.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+2383T>C		intron_variant		1	NM_005903.7	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54719 AN: 151980 Hom.: 10831 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.360 AC: 54794 AN: 152098 Hom.: 10860 Cov.: 32 AF XY: 0.356 AC XY: 26457 AN XY: 74350

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.385

Alfa AF: 0.327 Hom.: 1439

Bravo AF: 0.374

Asia WGS AF: 0.343 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	20
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs7356756; hg19: chr5-135471034;