rs4140535

Variant names:

• chr6-77465335-G-A
• rs4140535
• XM_047419658.1:c.-9298G>A

Variant summary

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

The XM_047419658.1(LOC105377864):​c.-9298G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,036 control chromosomes in the GnomAD database, including 11,089 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 0.38 (11089 hom., cov: 32)
• Consequence: LOC105377864 XM_047419658.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 16 publications found

Genes affected

LOC105377864 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377864	XM_047419658.1	c.-9298G>A		5_prime_UTR_variant	Exon 1 of 6		XP_047275614.1
LOC105377864	XM_047419659.1	c.-9124G>A		5_prime_UTR_variant	Exon 2 of 6		XP_047275615.1
LOC105377864	XM_047419660.1	c.-3742-9191G>A		intron_variant	Intron 5 of 8		XP_047275616.1
LOC105377864	XM_047419661.1	c.-3917+2217G>A		intron_variant	Intron 1 of 5		XP_047275617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296734	ENST00000741460.1	n.48+1565C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57492 AN: 151920 Hom.: 11091 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.378 AC: 57533 AN: 152036 Hom.: 11089 Cov.: 32 AF XY: 0.381 AC XY: 28326 AN XY: 74332

African (AFR) AF: 0.373 AC: 15453 AN: 41462

American (AMR) AF: 0.445 AC: 6790 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3268 AN: 5178

South Asian (SAS) AF: 0.416 AC: 2001 AN: 4806

European-Finnish (FIN) AF: 0.320 AC: 3382 AN: 10560

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24172 AN: 67976

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.368 Hom.: 2851

Bravo AF: 0.388

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4140535; hg19: chr6-78175052;