chr5-136134352-T-A

Position:

• chr5-136134352-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005903.7(SMAD5):​c.-245+1390T>A 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 152,056 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 NM_005903.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

SMAD5-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SMAD5	NM_005903.7	c.-245+1390T>A		intron_variant		ENST00000545279.6	NP_005894.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+1390T>A		intron_variant		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

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.384

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

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: rs10085013; hg19: chr5-135470041;