rs248999

Positions:

• chr5-80498283-A-G
• chr5-80498283-A-T

Variant summary

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

The NM_205548.3(FAM151B):​c.26-3509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,146 control chromosomes in the GnomAD database, including 59,246 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 0.88 (59246 hom., cov: 30)
• Consequence: FAM151B NM_205548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

FAM151B (HGNC:33716): (family with sequence similarity 151 member B) Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM151B	NM_205548.3	c.26-3509A>G		intron_variant		ENST00000282226.5	NP_991111.2
FAM151B	XM_011543234.3	c.73+3000A>G		intron_variant			XP_011541536.1
FAM151B	XM_011543235.3	c.25+10135A>G		intron_variant			XP_011541537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM151B	ENST00000282226.5	c.26-3509A>G		intron_variant		1	NM_205548.3	ENSP00000282226	P1
FAM151B	ENST00000502608.5	c.26-3509A>G		intron_variant, NMD_transcript_variant		3		ENSP00000427035
FAM151B	ENST00000507084.1	n.257-1602A>G		intron_variant, non_coding_transcript_variant		3
FAM151B	ENST00000511718.5	n.395-1602A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133418 AN: 152028 Hom.: 59213 Cov.: 30

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.877 AC: 133504 AN: 152146 Hom.: 59246 Cov.: 30 AF XY: 0.877 AC XY: 65209 AN XY: 74374

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.880

Alfa AF: 0.903 Hom.: 9375

Bravo AF: 0.873

Asia WGS AF: 0.889 AC: 3091 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	5.1
DANN	Benign	0.60

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: rs248999; hg19: chr5-79794102; COSMIC: COSV56472318; COSMIC: COSV56472318;