rs1844986

Positions:

• chr12-31322571-G-A
• chr12-31322571-G-T

Variant summary

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

The NM_001135812.2(SINHCAF):​c.-21+3453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,412 control chromosomes in the GnomAD database, including 2,216 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 0.15 (2216 hom., cov: 32)
• Consequence: SINHCAF NM_001135812.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

Genes affected

SINHCAF (HGNC:30702): (SIN3-HDAC complex associated factor) Involved in negative regulation of cell migration. Part of Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

SINHCAF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SINHCAF	NM_001135812.2	c.-21+3453C>T		intron_variant		ENST00000337682.9	NP_001129284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SINHCAF	ENST00000337682.9	c.-21+3453C>T		intron_variant		1	NM_001135812.2	ENSP00000337477.4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22400 AN: 151294 Hom.: 2218 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0722

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.148 AC: 22393 AN: 151412 Hom.: 2216 Cov.: 32 AF XY: 0.144 AC XY: 10659 AN XY: 73950

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0722

Gnomad4 EAS AF: 0.00234

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.134

Alfa AF: 0.127 Hom.: 296

Bravo AF: 0.136

Asia WGS AF: 0.0230 AC: 78 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.83

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: rs1844986; hg19: chr12-31475505;