rs3764942

Positions:

• chr5-136133811-C-T

Variant summary

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

The ENST00000509297.6(SMAD5):​c.-393C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 154,682 control chromosomes in the GnomAD database, including 869 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 0.097 (847 hom., cov: 32)
  • Exomes 𝑓: 0.12 (22 hom.)
• Consequence: SMAD5 ENST00000509297.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

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

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD5	NM_005903.7	c.-245+849C>T		intron_variant		ENST00000545279.6
SMAD5-AS1	NR_026763.1	n.1080G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD5	ENST00000545279.6	c.-245+849C>T		intron_variant		1	NM_005903.7	P1
SMAD5-AS1	ENST00000297163.3	n.1080G>A		non_coding_transcript_exon_variant	1/2	1
	ENST00000617906.1	n.116C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14657 AN: 151920 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.116 AC: 306 AN: 2644 Hom.: 22 Cov.: 0 AF XY: 0.105 AC XY: 142 AN XY: 1358

Gnomad4 AFR exome AF: 0.162

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0841

GnomAD4 genome AF: 0.0966 AC: 14683 AN: 152038 Hom.: 847 Cov.: 32 AF XY: 0.100 AC XY: 7456 AN XY: 74302

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0807 Hom.: 1159

Bravo AF: 0.0975

Asia WGS AF: 0.206 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.88

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: rs3764942; hg19: chr5-135469500; COSMIC: COSV51835714; COSMIC: COSV51835714;