rs12116935

Variant names:

• chr1-36323945-A-G
• rs12116935
• ENST00000474766.1:n.*1128A>G

Variant summary

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

The ENST00000474766.1(SH3D21):​n.*1128A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,222 control chromosomes in the GnomAD database, including 7,426 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 0.28 (7424 hom., cov: 33)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: SH3D21 ENST00000474766.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 27 publications found

Genes affected

SH3D21 (HGNC:26236): (SH3 domain containing 21) Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVA1B (HGNC:25558): (eva-1 homolog B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474766.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVA1B	NM_018166.3		c.-83T>C		5_prime_UTR	Exon 1 of 3	NP_060636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3D21	ENST00000474766.1	TSL:1	n.*1128A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000500135.1
	SH3D21	ENST00000474766.1	TSL:1	n.*1128A>G		3_prime_UTR	Exon 5 of 5	ENSP00000500135.1
	SH3D21	ENST00000373137.2	TSL:2	n.212A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43309 AN: 152088 Hom.: 7429 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

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) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.284 AC: 43296 AN: 152206 Hom.: 7424 Cov.: 33 AF XY: 0.284 AC XY: 21135 AN XY: 74410

African (AFR) AF: 0.102 AC: 4225 AN: 41556

American (AMR) AF: 0.256 AC: 3918 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3468

East Asian (EAS) AF: 0.0694 AC: 359 AN: 5172

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4830

European-Finnish (FIN) AF: 0.372 AC: 3934 AN: 10588

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26384 AN: 67980

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.353 Hom.: 41797

Bravo AF: 0.263

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		-0.35
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=299/1	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: rs12116935; hg19: chr1-36789546;