rs7333607

chr13-36887873-A-G

Variant summary

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

The NM_001127217.3(SMAD9):c.-186-7998T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,076 control chromosomes in the GnomAD database, including 4,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (★).

• Frequency: Genomes: 𝑓 0.23 (4309 hom., cov: 31)
• Consequence: SMAD9 NM_001127217.3 intron
• Clinical Significance: confers sensitivity criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.794

Genes affected

SMAD9 (HGNC:6774): (SMAD family member 9) The protein encoded by this gene is a member of the SMAD family, which transduces signals from TGF-beta family members. The encoded protein is activated by bone morphogenetic proteins and interacts with SMAD4. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD9	NM_001127217.3	c.-186-7998T>C		intron_variant		ENST00000379826.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD9	ENST00000379826.5	c.-186-7998T>C		intron_variant		5	NM_001127217.3	P1
SMAD9	ENST00000350148.10	c.-186-7998T>C		intron_variant		1
SMAD9	ENST00000483941.2	n.254-7998T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35499 AN: 151956 Hom.: 4308 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.234 AC: 35516 AN: 152076 Hom.: 4309 Cov.: 31 AF XY: 0.231 AC XY: 17200 AN XY: 74316

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0972

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.210

Alfa AF: 0.230 Hom.: 1155

Bravo AF: 0.227

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lung cancer Other:1

confers sensitivity, criteria provided, single submitter

research

Kong Lab, Department of Radiation Oncology, Case Western Reserve University School of Medicine

May 01, 2012

Improve the prediction accuracy for overal survival in non-small cell lung cancer patients -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.32
Dann	Benign	0.55

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: rs7333607; hg19: chr13-37462010;