rs1057898

Variant names:

• chr5-136181462-T-C
• rs1057898
• NM_005903.7:c.*3982T>C

Variant summary

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

The NM_005903.7(SMAD5):​c.*3982T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,922 control chromosomes in the GnomAD database, including 10,563 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 (10563 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: SMAD5 NM_005903.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 12 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.*3982T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.*3982T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_005903.7	ENSP00000441954.2
SMAD5	ENST00000545620.5	c.*3982T>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000446474.2
SMAD5	ENST00000513418.1	n.163-5699T>C		intron_variant	Intron 1 of 2	5		ENSP00000427650.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54157 AN: 151800 Hom.: 10535 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.357 AC: 54229 AN: 151916 Hom.: 10563 Cov.: 32 AF XY: 0.353 AC XY: 26179 AN XY: 74242

African (AFR) AF: 0.527 AC: 21831 AN: 41422

American (AMR) AF: 0.282 AC: 4306 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3464

East Asian (EAS) AF: 0.376 AC: 1940 AN: 5162

South Asian (SAS) AF: 0.185 AC: 893 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3188 AN: 10576

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

European-Non Finnish (NFE) AF: 0.292 AC: 19796 AN: 67882

Other (OTH) AF: 0.384 AC: 811 AN: 2110

Alfa AF: 0.321 Hom.: 3941

Bravo AF: 0.370

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	-0.72
CADD	Benign	8.9
DANN	Benign	0.83
PhyloP100		-0.65
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: rs1057898; hg19: chr5-135517150;