6-170404594-A-T

Variant names:

• chr6-170404594-A-T
• rs9295407
• NM_032448.3:c.*4A>T

Variant summary

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

The NM_032448.3(FAM120B):​c.*4A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,610,880 control chromosomes in the GnomAD database, including 9,946 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 0.13 (1605 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8341 hom.)
• Consequence: FAM120B NM_032448.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 11 publications found

Genes affected

FAM120B (HGNC:21109): (family with sequence similarity 120 member B) Predicted to be involved in fat cell differentiation and peroxisome proliferator activated receptor signaling pathway. Predicted to be active in nucleus. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	NM_032448.3	MANE Select	c.*4A>T		3_prime_UTR	Exon 10 of 11	NP_115824.1	Q96EK7-1
	FAM120B	NM_001286380.2		c.*4A>T		3_prime_UTR	Exon 10 of 11	NP_001273309.1	F5GY05
	FAM120B	NM_001286379.2		c.*4A>T		3_prime_UTR	Exon 10 of 11	NP_001273308.1	A0A0D9SEJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	ENST00000476287.4	TSL:1 MANE Select	c.*4A>T		3_prime_UTR	Exon 10 of 11	ENSP00000417970.1	Q96EK7-1
	FAM120B	ENST00000537664.5	TSL:2	c.*4A>T		3_prime_UTR	Exon 10 of 11	ENSP00000440125.1	F5GY05
	FAM120B	ENST00000630384.2	TSL:2	c.*4A>T		3_prime_UTR	Exon 10 of 11	ENSP00000485745.1	A0A0D9SEJ5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20124 AN: 152026 Hom.: 1602 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.0956 AC: 23965 AN: 250794 AF XY: 0.0939

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.0639

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.0582

Gnomad FIN exome AF: 0.0670

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.102 AC: 148184 AN: 1458736 Hom.: 8341 Cov.: 29 AF XY: 0.101 AC XY: 72997 AN XY: 725922

African (AFR) AF: 0.225 AC: 7518 AN: 33370

American (AMR) AF: 0.0672 AC: 3001 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3475 AN: 26088

East Asian (EAS) AF: 0.0496 AC: 1969 AN: 39674

South Asian (SAS) AF: 0.0671 AC: 5780 AN: 86116

European-Finnish (FIN) AF: 0.0663 AC: 3538 AN: 53384

Middle Eastern (MID) AF: 0.176 AC: 1014 AN: 5756

European-Non Finnish (NFE) AF: 0.104 AC: 115029 AN: 1109414

Other (OTH) AF: 0.114 AC: 6860 AN: 60286

GnomAD4 genome AF: 0.132 AC: 20155 AN: 152144 Hom.: 1605 Cov.: 33 AF XY: 0.128 AC XY: 9515 AN XY: 74392

African (AFR) AF: 0.220 AC: 9106 AN: 41474

American (AMR) AF: 0.103 AC: 1575 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5178

South Asian (SAS) AF: 0.0696 AC: 335 AN: 4812

European-Finnish (FIN) AF: 0.0710 AC: 753 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7076 AN: 67992

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.0635 Hom.: 109

Bravo AF: 0.140

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.112

EpiControl AF: 0.115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9295407; hg19: chr6-170713682; COSMIC: COSV53009645;