rs6596286

Variant names:

• chr5-136142032-C-T
• rs6596286
• NM_005903.7:c.-244-5800C>T

Variant summary

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

The NM_005903.7(SMAD5):​c.-244-5800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,956 control chromosomes in the GnomAD database, including 10,541 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 (10541 hom., cov: 32)
• Consequence: SMAD5 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.-244-5800C>T		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.-244-5800C>T		intron_variant	Intron 1 of 7	1	NM_005903.7	ENSP00000441954.2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54110 AN: 151838 Hom.: 10513 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.357 AC: 54183 AN: 151956 Hom.: 10541 Cov.: 32 AF XY: 0.352 AC XY: 26168 AN XY: 74260

African (AFR) AF: 0.526 AC: 21796 AN: 41412

American (AMR) AF: 0.281 AC: 4290 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1945 AN: 5178

South Asian (SAS) AF: 0.187 AC: 901 AN: 4820

European-Finnish (FIN) AF: 0.302 AC: 3177 AN: 10536

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19803 AN: 67980

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.325 Hom.: 1160

Bravo AF: 0.369

Asia WGS AF: 0.342 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.59
PhyloP100		-0.99
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: rs6596286; hg19: chr5-135477721;