12-50086152-C-T

Variant names:

• chr12-50086152-C-T
• rs2307082
• NM_003076.5:c.178-9C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003076.5(SMARCD1):​c.178-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,530,350 control chromosomes in the GnomAD database, including 871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (256 hom., cov: 31)
  • Exomes 𝑓: 0.012 (615 hom.)
• Consequence: SMARCD1 NM_003076.5 intron
• Scores: Splicing: ADA: 0.00001052
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.171

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 12-50086152-C-T is Benign according to our data. Variant chr12-50086152-C-T is described in ClinVar as [Benign]. Clinvar id is 1283034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.178-9C>T		intron_variant	Intron 1 of 12	ENST00000394963.9	NP_003067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9	c.178-9C>T		intron_variant	Intron 1 of 12	1	NM_003076.5	ENSP00000378414.4

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5681 AN: 152078 Hom.: 251 Cov.: 31

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0355

GnomAD2 exomes AF: 0.0330 AC: 6506 AN: 197228 AF XY: 0.0291

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.00959

Gnomad EAS exome AF: 0.0540

Gnomad FIN exome AF: 0.000766

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.0226

GnomAD4 exome AF: 0.0118 AC: 16313 AN: 1378154 Hom.: 615 Cov.: 31 AF XY: 0.0123 AC XY: 8352 AN XY: 676982

Gnomad4 AFR exome AF: 0.0956 AC: 2960 AN: 30950

Gnomad4 AMR exome AF: 0.104 AC: 3452 AN: 33212

Gnomad4 ASJ exome AF: 0.00779 AC: 164 AN: 21042

Gnomad4 EAS exome AF: 0.0724 AC: 2810 AN: 38822

Gnomad4 SAS exome AF: 0.0450 AC: 3351 AN: 74432

Gnomad4 FIN exome AF: 0.000891 AC: 45 AN: 50488

Gnomad4 NFE exome AF: 0.00228 AC: 2429 AN: 1067254

Gnomad4 Remaining exome AF: 0.0174 AC: 982 AN: 56578

GnomAD4 genome AF: 0.0374 AC: 5689 AN: 152196 Hom.: 256 Cov.: 31 AF XY: 0.0381 AC XY: 2834 AN XY: 74418

Gnomad4 AFR AF: 0.0939 AC: 0.0939127 AN: 0.0939127

Gnomad4 AMR AF: 0.0642 AC: 0.0641746 AN: 0.0641746

Gnomad4 ASJ AF: 0.00952 AC: 0.00951557 AN: 0.00951557

Gnomad4 EAS AF: 0.0545 AC: 0.0545033 AN: 0.0545033

Gnomad4 SAS AF: 0.0450 AC: 0.0450207 AN: 0.0450207

Gnomad4 FIN AF: 0.00104 AC: 0.00103695 AN: 0.00103695

Gnomad4 NFE AF: 0.00278 AC: 0.00277884 AN: 0.00277884

Gnomad4 OTH AF: 0.0346 AC: 0.03463 AN: 0.03463

Alfa AF: 0.0272 Hom.: 90

Bravo AF: 0.0457

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Coffin-Siris syndrome 11 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.9
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.020		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: rs2307082; hg19: chr12-50479935;