rs6453086

Variant names:

• chr5-74811789-G-A
• rs6453086
• NM_001376049.1:c.670+2051C>T

Variant summary

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

The NM_001376049.1(FAM169A):​c.670+2051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,080 control chromosomes in the GnomAD database, including 7,489 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 0.29 (7489 hom., cov: 32)
• Consequence: FAM169A NM_001376049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 7 publications found

Genes affected

FAM169A (HGNC:29138): (family with sequence similarity 169 member A) Predicted to be located in nuclear inner 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM169A	NM_001376049.1	c.670+2051C>T		intron_variant	Intron 6 of 12	ENST00000687041.1	NP_001362978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM169A	ENST00000687041.1	c.670+2051C>T		intron_variant	Intron 6 of 12		NM_001376049.1	ENSP00000508577.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43516 AN: 151962 Hom.: 7473 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.287 AC: 43574 AN: 152080 Hom.: 7489 Cov.: 32 AF XY: 0.284 AC XY: 21092 AN XY: 74350

African (AFR) AF: 0.482 AC: 20009 AN: 41494

American (AMR) AF: 0.302 AC: 4610 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.186 AC: 961 AN: 5176

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4814

European-Finnish (FIN) AF: 0.148 AC: 1566 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13708 AN: 67960

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.252 Hom.: 9712

Bravo AF: 0.308

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.38
PhyloP100		0.40
Mutation Taster		=100/0	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: rs6453086; hg19: chr5-74107614; COSMIC: COSV65847168; COSMIC: COSV65847168;